Abstract
The bacterial groups in the gut ecosystem play key role in the maintenance of host’s metabolic and structural functionality. The gut microbiota enhances digestion processing, helps in digestion of complex substances, synthesizes beneficial bioactive compounds, enhances bioavailability of minerals, impedes growth of pathogenic microbes, and prevents various diseases. It is, therefore, desirable to have an adequate intake of prebiotic biomolecules, which promote favorable modulation of intestinal microflora. Prebiotics are non-digestible and chemically stable structures that significantly enhance growth and functionality of gut microflora. The non-digestible carbohydrate, mainly oligosaccharides, covers a major part of total available prebiotics as dietary additives. The review describes the types of prebiotic low molecular weight carbohydrates, i.e., oligosaccharides, their structure, biosynthesis, functionality, and applications, with a special focus given to fructooligosaccharides (FOSs). The review provides an update on enzymes executing hydrolytic and fructosyltransferase activities producing prebiotic FOS biomolecules, and future perspectives.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
A microbial ecosystem in human gut plays crucial roles in digestion process [1]. The diverse microbial population in human digestive track, especially in colon, makes it metabolically more active. Colon, in the lower digestive tract, is involved in the breakdown of complex carbohydrates, dietary components, and some proteins that remains to be hydrolyzed in the upper digestive tract. The gut microbiota has a significant impact on human health; however, a major proportion, approximately 50%, of this microbial cosmos is non-cultivable [2,3,4]. It is important to modulate the gut microflora to enhance beneficial metabolic activities in the intestine. There are two possible ways to alter colonic microflora supplementation of live microbes, known as probiotics, or consumption of non-digestible food ingredients that stimulate growth and/or activity of microbes in the gut, called as prebiotics [5].
Prebiotics are non-digestible carbohydrates that are chemically stable at wide temperature and pH ranges [3]. Prebiotics are resistant to hydrolytic actions of intestinal enzymes but are fermentable by the intestinal beneficial microbes and, therefore, gives growth-promoting effects on beneficial microbes such as Bifidobacterium sp. and Lactobacillus sp. [2]. The colonic bacteria ferment these non-digestible dietary carbohydrates, producing a wide range of metabolites in gut, e.g., short-chain fatty acids [5]. The volatile short-chain (1–6 carbon), straight or branched, fatty acids exert crucial physiological implications, such as concomitant reduction of the luminal pH that inhibit the growth of pathogenic microorganisms, host signaling, and bacterial cross-feeding interactions [6,7,8,9].
Generally, all prebiotics fall under the category of dietary fibers but all dietary fibers are not prebiotic. The key prebiotics are inulin, fructooligosaccharides (FOSs), glucooligosaccharides (GuOSs), galactooligosaccharides (GaOSs), xylooligosaccharides (XOSs), maltooligosaccharides (MOs), isomaltooligosaccharides (IMOs), lactulose, lactosucrose, raffinose, stachyose, lactulosucrose, fructans, resistant starch, etc. [2, 6, 9] (Table 1). Inulin, FOS, and GaOS are the most popular prebiotics used in different food products, including baby foods [6]. The natural sources for prebiotics are plants, honey, and milk (Table 2). Prebiotics can be produced by enzymatic hydrolysis of polymers, e.g., oligofructose from inulin or by oligosaccharide synthesis through transglycosylation reactions [3, 4] (Tables 2 and 3). The structure of oligosaccharide, including the nature of gylcosidic bonds, its solubility, viscosity, fermentability, and degree of polymerization (DP) are important coordinates for determining the functionality of a prebiotic [4]. Prebiotic oligosaccharides are helpful in minimizing health-related risks, such as diabetes, cardiovascular disorders, cancer, acute infection, inflammation, and obesity. Prebiotic consumption also enhances bioavailability of nutritionally important minerals such as calcium, magnesium, and iron [33]. Different probiotic microbes employ different genetic mechanisms for utilizing different types of oligosaccharides; therefore, the extent of efficacy of dietary fibers on health is dependent on the type of prebiotic biomolecule consumed [34].
The aim of the present review is to summarize the background information pertaining to different prebiotic oligosaccharides with a major focus on fructooligosaccharides.
Types of Prebiotic Oligosaccharides
Galactooligosaccharides
Galactooligosaccharides are galactose-containing oligosaccharides having β (1–3) and β (1–4) bonds among the monomers, synthesized by transgalactosylase activity of β-galactosidase enzyme utilizing lactose [35]. It has a bifidogenic property with a profound effect on Bifidobacterium sp. level in the gut [36]. It can tolerate high temperature and low pH and, therefore, is preferred additive in food products [35]. It is also used in infants’ milk as functional ingredients exerting health-promoting effects. The mixture of 90% short-chain galactooligosaccharides along with 10% long-chain fructooligosaccharides are used in human milk to mimic the molecular size distribution of natural oligosaccharides [37, 38].
Xylooligosaccharides
Xylooligosaccharide is the new emerging prebiotics used as functional food products in pharmaceutical, nutraceutical, and agriculture sectors [39]. Xylooligosaccharide is made up of xylose monomeric units having β (1–4) glycosidic linkage. The xylan and arabinoxylan polysaccharides, widely distributed in plants, are key feedstock for xylooligosaccharide production. Xylooligosaccharide can be synthesized by enzymatic hydrolysis or chemical fractionation of lignocellulosic materials [40]. At present, xylooligosaccharide is commercially produced from corn cob employing xylanase enzyme [4].
Malto- and Isomaltooligosaccharides
Maltooligosaccharides are composed of a chain of glucose monomers linked with α (1–4) linkages. These can be produced from polysaccharides such as starch, glycogen, and amylose by the catalytic actions of debranching enzymes, amylases, and pullulanase. Maltooligosaccharides are susceptible to the intestinal enzymes and are generally absorbed in the small intestine. Though maltooligosaccharides are less effective in the growth of Bifidobacteria, they can reduce the level of putrefactive bacteria in the intestine [41]. Isomaltooligosaccharides (IMO) are oligomers of glucose with generally α (1–6) bonds, and sometimes with α (1–2) or α (1–3) or α (1–4) linkages. The IMO include different oligomers, e.g., isomaltose, panose, isomaltotriose, isomaltotetraose, isomaltopentaose, nigerose, kojibiose, and other highly branched oligosaccharides. Traditionally, IMO is synthesized from starch by enzymatic actions of α-amylase, β-amylase, or pullulanase, generating maltose and maltotriose, followed by transglycosylation activity by α-transglucosidase [42]. Basu et al. established simultaneous saccharification and transglucosylation approach for production of isomaltooligosaccharides from starch [43]. However, this approach generally yields a mixture of glucooligosaccharides containing both α (1–6) and α (1–4) glycosidic bonds [44].
Transglycosidation reaction by glucosyltransferases also results biosynthesis of IMO. Glucose moiety is transferred to its accepter molecules such as maltose or isomaltose or O-α-methylglucoside to produce glucooligosaccharide. Leuconostoc mesenteroides is a well-known microbe to produce enzymes, such as mutansucrases, dextransucrases, alternansucrases, or reuteransucrases, with catalytic efficiency of glucooligosaccharide biosynthesis [45,46,47].
Dextransucrase catalyzes hydrolysis of sucrose, followed by transfer of glucose unit from sucrose to acceptor molecules, synthesizing IMO [48]. In the presence of suitable acceptor molecules, such as maltose or isomaltose, dextransucrase catalyzes IMO synthesis. This approach yields oligosaccharides with nearly exclusive α (1–6) glycosidic bonds among glucose moieties [49]. In addition, dextransucrase also catalyzes polysaccharide (dextran) synthesis using the growing glucan chain as acceptor [45]. A continuous synthesis process has been developed for production of IMO and oligodextrans from sucrose using dextransucrase and dextranase enzymes [50].
Gentiooligosaccharide
Gentiooligosaccharide is composed of glucose units linked with β (1–6) bond. Apart from being prebiotic, its bitter taste is useful to generate a specific taste in certain beverages. Gentiooligosaccharide biosynthesis is catalyzed by two methods, transglycosylation and glycosyltransferase activities. The combination of β-glucosidase, which produces gentiotriose from gentiobiose, and β (1–6) glucanase enzymes, in the case of which gentiotriose is both donor and acceptor, can efficiently synthesize gentiooligosaccharides [51, 52].
Gentiooligosaccharides may also be synthesized by glycosyltransferase reactions executed by dextransucrase taking sucrose as substrate, in presence of gentiobiose (acceptor) molecules [53]. Further, gentiooligosaccharides can be obtained by hydrolysis of lichen polysaccharide, pustulan [54]. Gentiooligosaccharides enhances the growth of Bifidobacterium infantis and Lactobacillus acidophilus in the gut and have almost similar digestibility in comparison to the standard prebiotics.
Chitosan Oligosaccharides and Cyclodextrins
Chitosan is a derivative of chitin, composed of d-glucosamine and N-acetyl-d-glucosamine units joined by β (1–4) glycosidic linkages. Chitosan oligosaccharides are produced by chemical (high temperature and low pH) or enzymatic (chitosanases) hydrolysis of the chitosan polysaccharides [55]. Their consumption promotes the growth of colon bacteria (e.g., Bifidobacterium sp.), therefore, useful in the food industry [56]. Additionally, chitosan oligosaccharides and cyclodextrins exert various biomedical benefits such as antitumor, antimicrobial, anti-inflammatory, antioxidant, and immuno-enhancing effects [57].
Cyclodextrin is a cyclic oligosaccharide composed of glucose molecules linked with cyclic α (1–4) bonds. It is biosynthesized from starch by the amylolytic enzyme, cyclodextrin glucosyltransferase, which catalyzes transglycosylation, intramolecular cyclization, and intermolecular coupling reactions [51].
Pectin-Derived Oligosaccharides
The complex heteropolysaccharide, pectin, has been found to have the potential of a prebiotic substance. The oligosaccharides are produced by partial depolymerization of pectin by acid or enzymatic hydrolysis, hydrothermal processing, and physical degradation [58, 59]. Pectic oligosaccharide is composed of d-galacturonic acid (GalA) units, present in either its acetylated or methylated forms, linked by α (1–4) bonds. They include several categories of oligosaccharides such as galactooligosaccharide, arabinogalactooligosaccharide, rhamnogalacturonooligosaccharide, oligogalacturonide, and arabinooligosaccharide. Apart from having prebiotic potential, these oligosaccharides exhibit antiulcer, anticancer, antiobesity, and anti-inflammatory properties [60].
The pectin from sugar beet is known to be rich in arabinan fraction [61]. Endoarabinanases are employed to hydrolyze arabinan into arabinooligosaccharides. The l-arabinosyl residues are linked with α (1–5) or α (1–2) or α (1–3) bonds [62]. It has been observed to significantly increase the population of beneficial gut microbes such as Bifidobacterium sp. [63]. Endogalactanases can generate arabinogalactooligosaccharide from soybeans, rhamnogalacturonase can produce rhamnogalacturonooligosaccharide from apple, and arabinoxylooligosaccharide can be made by employing xylanases on wheat biomass [55, 64].
Agarooligosaccharide and Neo-agarooligosaccharide
Agarooligosaccharide and neo-agarooligosaccharide are produced from agar by hydrolytic activities of α-agarase and β-agarase enzymes [65]. In agarooligosacharides, 3,6-anhydro-l-galactose and d-galactose units are linked by α (1–3) and β (1–4) glycosidic bonds. Agarooligosaccharide and neo-agarooligosaccharide are able to boost the growth of gut bacteria such as Bifidobacteria sp. and Lactobacilli sp. [66]. They also exhibit other health-promoting activities, such as anti-inflammatory, antitumor, and antioxidant properties [65].
Raffinose, Stachyose, and Verbascose
Raffinose, stachyose, and verbascose are tri-, tetra-, and pentasaccharides, respectively. These oligosaccharides are found in Glycine max in substantial amount (e.g., 2–6% raffinose and 1–2% stachyose (w/w) of dry mass). In these oligosaccharides, galactose units are linked to sucrose by α (1–6) glycosidic bonds. Raffinose is composed of galactose, glucose, and fructose, whereas stachyose contains two galactose, one glucose, and one fructose molecule. The raffinose and stachyose are biosynthesized from sucrose by galactosyltransferases enzymes known as raffinose synthase and stachyose synthase, respectively [67]. Verbascose is composed of three galactose, and one glucose and fructose molecules. Stachyose synthase catalyzes synthesis of verbascose. The soybean oligosaccharides are generally obtained from soybean whey, a by-product generated during production of soy protein [40]. The soybean oligosaccharides are considered as effective prebiotic biomolecules for functional food applications.
Lactulose, Lactosucrose, Glycosylsucrose, and Isomaltulose
Lactulose is a ketose disaccharides synthesized from lactose, in which glucose moiety is isomerized into fructose. In lactulose, the units are joined by β (1–4) glycosidic linkage. It can be synthesized by catalytic actions of β-galactosidase and glucose isomerase enzymes using whey lactose [68]. In milk, lactose can also be transformed into lactulose by moderate heating [69]. It is not digestible in the intestine and can stimulate growth of Lactobacilli sp. and Bifidobacteria sp. bacteria; on the other hand, it decreases the growth of clostridia, coliforms, streptococci, and bacteroides in the gut [4].
Lactosucrose (4(G)-beta-d-galactosylsucrose) is composed of galactose, glucose, and fructose with β (1–4) and α (1–2) glycosidic bonds. The trisaccharide is synthesized by transfructosylation reaction catalyzed by levansucrase or β-fructofuranosidase enzyme utilizing lactose and sucrose [70]. Lactosucrose enhances mineral absorption in the gut and also aid in growth of gut microbiota. It inhibits intestinal lipid absorption and, thus, helps in preventing obesity. It is preferred to be used as an ingredient in desserts, sweets, confectioneries, yogurts, tea, coffee, etc. [71].
Glycosylsucrose, also known as coupling sugar, is a trisaccharide produced from sucrose and maltose via the transglycosylation activity of the cyclomaltodextrin glucanotransferase enzyme. Unlike sucrose, it does not cause dental caries and extends other benefits to food processing applications. However, it is lesser bifidogenic responsive as compared to other prebiotics [40, 41].
Isomaltulose, also known as palatinose, is a disaccharide in which glucose and fructose are linked by α (1–6) glycosidic linkages. Thus, it is a structural isomer of sucrose, synthesized via rearrangement of the glycosidic linkage in sucrose. It naturally occurs in honey and sugarcane juice and is considered to be a potential prebiotic molecule [40, 51].
Fructooligosaccharides
Fructooligosaccharide is one of the most explored prebiotics [72]. The low-calorie FOS, besides being prebiotic, helps in reducing cholesterol level, inhibiting the growth of harmful bacteria and improving mineral absorption in the gut. FOS is composed of one glucose moiety followed by fructose moieties ranging from 2 to 60 linked by β (2–1) or β (2–6) glycosidic bonds, for example, 1-kestose (one glucose and two fructose), nystose (one glucose and three fructose), and fructofuranosyl nystose (one glucose and four fructose) [73, 74]. FOS is not digested in the small intestine but gets metabolized in cecum into small-chain fatty acid and l-lactate, and other bioactive molecules beneficial to human health [2]. FOS enhances absorption of minerals such as Mg+2 and Ca+2 and decreases fatty acid level in the gut [75]. As fructan biosynthesis occurs in plants and fungi, besides in bacteria, the potential plant sources of FOS are Triticum sp., Allium cepa, Allium sativum, Secale cereal, Solanum lycopersicum, Asparagus officinalis, Cichorium intybus, Musa sp., and Helianthus tuberosus [4, 76]. The commercial market of prebiotics is at present dominated by inulin (polymer of fructose), FOS, GaOS, and IMO. The inulin, oligofructose (produced by hydrolysis of inulin), or FOS are extensively studied prebiotics, and several reports suggest that use of fructans in diet stimulates gut microbes more effectively. FOS is commercially used as a food ingredient and publically available under several trade names like Neosugar, NutraFlora®, Meioligo®, and Actilight® [72].
Fructooligosacharides: Properties, Synthesis, and Applications
Physiochemical Properties of Fructooligosaccharide
FOS, being water soluble, hygroscopic and relatively less sweet, and of reduced caloric value and prebiotic in nature, are useful ingredients in food industry [77]. Sweetness of FOS decreases with increase in the degree of polymerization [78]. FOS is composed of fructose monomers linked together with a terminally attached glucose unit, i.e., glucose-(fructose)n (Fig. 1). On the basis of chemical structure, FOS may be categorized in different types, such as inulin-FOS (1F-FOS), levan FOS (6F-FOS), and neo-FOS (6G-FOS) [64, 79]. These types differ by the nature of glycosyl bonds among the monomer units, for example, fructose units are linked by linear β (2–1) and β (2–6) in inulin- and levan-type FOS, respectively. Commercially available inulin-FOS includes 1-kestose (lF-β-d-fructofuranosylsucrose) (GF2), 1-nystose [1F (1F-β-d-fructofuranosyl)2 sucrose] (GF3), and lF-β-fructofrcutofuranosyl nystose (GF4). In neo-FOS, glucose moiety of sucrose is linked to fructose unit via β (2–6) linkage in branched manner, which generates the possibilities for elongation of fructose chain in both β (2–1) and β (2–6) orientations [79]. Examples of neo-FOS are neo-kestose (neo-GF2), neo-nystose (neo-GF3), and neo-frcutofuranosyl nystose (neo-GF4). Neo-FOS has superior prebiotic activity as well as stability in comparison to 1F-FOS [80].
An overview of reactions catalyzed by FTases for synthesis of fructooligosaccharides and biopolymers (levan and inulin). Enzymes are highlighted in red color. 1-SST sucrose:sucrose 1-fructosyl-transferase, 1-FFT fructan:fructan 1-fructosyltransferase, 6-SST sucrose:sucrose 6-fructosyltransferase, 6-FFT fructan:fructan 6-fructosyltransferase, G6−FFT fructan:fructan 6G-fructosyltransferase, 6-SFT sucrose:fructan 6-fructosyltransferase, ExI exoinulinases, EnI endoinulinase, EnLev endolevanase, ExLev exolevanase
For decades, researchers are engaged in mining the strategies for production of FOS [81]. Fructans have been successfully extracted from plant sources such as Cichorium intybus (chikori), Allium cepa (onion), and Helianthus tuberosus (Jerusalem artichoke) for FOS production. However, isolation and downstream processing of FOS from these natural sources is tedious and costly (Table 4) [10]. The stereospecificity of glycosidic bond formation between the monomeric units of FOS makes its chemical synthesis a challenging process [95]. Biotechnological approaches can provide an efficient and productive platform for FOS production. Here, we have reviewed the sources having genetic potential for biosynthesis of FOS at pilot scale.
Biotechnological Approach for Efficient Production of Oligosaccharide
The enzymatic method for production of FOS is a cost- and time-effective process that can be exploited at industrial scale. The enzymatic sources have been reported from different organisms catalyzing the biosynthesis of FOS with different degree of polymerization and/or glycosidic linkages (Tables 4, 5, and 6). The following methods of catalytic production of FOS have been explored.
Biosynthesis of Fructooligosaccharide from Sucrose
The enzymes that execute catalytic biosynthesis of FOS using sucrose as substrate are known as frutosyltransferases (EC 2.4.1.99) or β-fructofuranosidases (EC 3.2.1.26) [138]. Even after a long debate, still the dilemma exists in the nomenclature of these enzymes. Fructosyltransferases (FTases) catalyze the transfructosylation of sucrose, which includes hydrolysis of sucrose molecule followed by transfer of liberated fructose unit to an acceptor molecule such as sucrose or other fructooligosaccharide like molecule. FTases break α (1–2) linkage in sucrose and transfer the liberated fructose molecule at either β (2–1) or β (2–6) position of fructose unit of another sucrose molecule. Generally, the transfer of fructose moiety does not happen to the free glucose or water molecules present in the reaction mixture. At the end, the reaction mix contains several components including some unreacted sucrose, glucose, fructose, and oligosaccharides of different degree of polymerization. The nature of FOS may also vary under variable reaction conditions. Some FTases catalyze synthesis of FOS only, but not the polymer [79, 81, 138]. FTase from Aspergillus aculeatus catalyzes the synthesis of short-chain FOS (kestose, nystose, and fructosylnystose), while levansucrase not only synthesizes FOS but also produce polymers of fructose, called as levan [97, 121]. FTases possess both hydrolytic and transfructosylation activities, depending upon the concentration of sucrose. In case of high sucrose concentration, increased transfructosylation activity has been observed [139]. The extent of hydrolyitc or transfructosylating activities differs with different enzymes. FTases have been reported in plants, bacteria, and fungi.
Plant Fructosyltransferase
About 15% flowering plants have the mechanism for biosynthesis of fructans, the linear or branched chain of fructose (Table 2) [140]. Depending on the nature of firstly synthesized triscaharide, these are divided into five distinct groups: (1) inulin (Astarales), (2) levan (Poales), (3) neo-inulin (Asparagales), (4) neo-levan (Poales), and (5) graminans (Poales) [141]. For synthesis of inulin-type fructans in plants, two enzymes are required: (i) sucrose, sucrose 1-fructosyl-transferase (1-SST); (ii) fructan, fructan 1-fructosyltransferase (1-FFT) [90]. 1-SST hydrolyzes one sucrose molecule and transfers the fructose moiety onto fructose of another sucrose molecule, consequently forming a trisaccharide, 1-kestose (DP-3). Thus, two molecules of sucrose are utilized in this mechanism. Another enzyme, 1-FFT, transfers fructose to other fructan molecules (e.g., 1-kestose and inulin) at the fructose moiety of the 1-kestose, generating 1-nystose (DP-4), or oligosaccharide of higher DP, and subsequently inulin (DP ≥ 25). Thus, 1-FFT functions through breaking and reconstructing the β (2–1) linkage (Fig. 1) [142]. The preferred donor substrate for 1-FFT could be 1-kestose and inulin. Genes encoding 1-SST and 1-FFT enzymes have been identified in plants [83, 143]. In plants, which synthesizes levan-type fructans, enzymes are yet to be fully explored. Plants possess either single enzyme, sucrose:fructan 6-fructosyltransferase (6-SFT), or sometimes more than one enzymes that may be more specific in their functions. For example, sucrose:sucrose 6-fructosyltransferase (6-SST) catalyzes the synthesis of 6-kestose, and fructan:fructan 6-fructosyl-transferase (6-FFT) is responsible for the synthesis of levan-type fructan through elongation of 6-kestose by transferring fructose moieties [144]. Existence of 6-SFT in plants is reported, but there is uncertainty about the 6-SST/6-FFT [144, 145]. Another enzyme is fructan:fructan 6-glucose-fructosyl-transferase (G6-FFT), which produces neo-type fructans by transferring glucose unit to fructose moiety through β (2–6) linkage [73, 146]. In plants, fructan synthesis occurs via a complex process. Further, it is difficult to isolate and purify the enzymes of plant origin, although attempts have been made for isolation and purification of enzymes from plants such as from asparagus, onion, and artichoke [143, 147]. Heterologous expression of plant genes in microbial cells could be one way for industrial application of these genes; however, heterologous expression of plant genes faces challenges related to codon optimization and appropriate protein folding [148, 149].
Fungal and Bacterial Fructosyltransferases
Since last three decades, many fungal and bacterial species have been explored that express FTases [96, 106]. Interestingly, microbial FTases have both hydrolytic and transferase activities within one enzyme [11]. Several fungal organisms are reported to have FTase activity, such as Aureobasidium pullulans (CFR 77), Aureobasidium sp. P6, Aspergillus japonicas, Schwanniomyces occidentalis, Penicillium citrinum, and Xanthophyllomyces dendrorhous [96, 100, 106, 110, 150, 151]. In Tables 5 and 6, fungal and bacterial sources for FTase have been presented. However, specificity and properties of the enzyme vary from one species to another species (Tables 5 and 6). Generally, FTases from bacterial sources have ~ 45–65-kDa molecular weight, but in lactic acid-producing bacteria (LAB), FTases are of high molecular weight ranging from 60 to 170 kDa [152, 153]. Many FTases are isolated and characterized from the probiotic lactic acid-producing bacteria such as L. reuteri, L. johnsonii, and L. gasseri. Recently, the newly identified group of levansucrase enzyme in fungi and bacteria (EC 2.4.1.10) attracted attention for the catalytic synthesis of β (2–6) linked FOS and levan with higher DP using sucrose as substrate [154]. Levansucrases have been isolated and characterized from different gram-positive and gram-negative bacteria. Many LAB have been found to have FTases, such as Streptococcus salivarius, Leuconostoc mesenteroids, Leuconostoc citreum Strain BD1707, and Lactobacillus reuteri [129, 152]. Some non-lactic acid-producing bacteria (NLAB) representing levensucrase production are Bacillus polymyxa, Zymomonas mobilis, Erwinia amylovora, Acetobacter diazotrophicus, and Bacillus amyloliquefaciens [137, 155,156,157,158]. The efficiency of the enzyme makes them worthy of their use at industrial scale for producing the FOS as well as levan.
Inulosucrase catalyzes formation of β (2–1) linked oligosaccharides and inulin polymer from sucrose. Inulosucrases have been isolated from gram-positive bacteria, such as S. mutans, Leuconostoc citrinum, Lactobacillus johnsonii NCC 533, Bacillus sp., Leuconostoc citreum CW28, and Lactobacillus gasseri DSM 20604 [114, 135, 153, 158, 159]. Application of FTases is limited by its inhibition in the presence of glucose, a by-product of the fructosyltransferase reaction. Therefore, it becomes crucial to remove glucose from the reaction mixture by its transformation into isomers, employing other enzymes, such as glucose isomerase and glucose oxidase. Glucose oxidase is relatively more effective in obtaining a higher yield of FOS [160, 161]. However, the attempts of enzyme engineering are required to improve the traits of FTases so that its activity should not be compromised in the presence of excess glucose.
Synthesis of Fructooligosaccharide from Levan
Levan is a polymer of d-fructose linked by β (2–6) linkages. Levanases exhibits gylcosyl hydrolase activity leading to FOS production. It has higher substrate specificity for levan, followed by inulin [162, 163]. It has been isolated and characterized from several bacterial sources like Bacillus subtilis, Rhodotorula sp., Streptococcus salivarius KTA-19, Streptomyces sp., and Gluconacetobacter diazotrophicus SRT4 [102, 162,163,164,165]. The endolevanse from B. subtilis 168, which is known to exhibit high level specificity towards β (2–6) linkages, has substrate acceptability for bacterial and grass-type levan, but unable to catalyze inulin as substrate [166].
Synthesis of Fructooligosaccharide from Inulin
Inulin is a polymer of fructosyl units that are linked by β (2–1) bonds, with one terminally joined glucose unit through α (1–2) linkage. Inulinases, enzymes of GH 32 family, cleave β (2–1) linkages in inulin, generating FOS. On the basis of cleavage pattern, inulinases are of two types: (i) exoinulinase (EC 3.2.1.80) catalyzes the terminal fructose unit and releases free fructose from inulin and (ii) endoinulinase (EC 3.2.1.7) catalyzes random cleavage of β (2–1) glycosidic bonds within inulin, and thus generating FOS of different chain length, e.g., inulotriose (F3), inulotetrose (F4), and inulopentose (F4). In contrast, exoinulinases are useful in production of high fructose syrup [125, 167]. Inulinases, both extracellular and intracellular, have been reported from a large number of organisms, including bacteria, fungi, and yeast (Tables 4 and 5).
Substrates and Acceptors Specificity of Enzymes for Synthesis of Fructooligosaccharide
The FOS derived from the same substrate (i.e., sucrose) may differ chemically due to differential action of enzymes, creating different types of glycosidic linkages. The concentration of sucrose in the reaction also affects the enzymatic activity, especially in the cases where both hydrolytic and transferase activities are present in the same enzyme. These enzymes are comfortable with a range of acceptor molecules for the transfer of fructofuranose ring. A number of acceptors have been reported for them such as water, sucrose, raffinose, maltose, maltotriose, arabinose, sorbitol, and xylose [125, 168, 169]. B. subtilis NCIMB 11871 FTase catalyzes synthesis of sucrose analogue (Gal-Fru), utilizing the substrates, sucrose, raffinose, and stachyose, by transfer of β-fructofuranosyl moiety to C-1 position of galactopyranoside [170]. Levansucrase from B. subtilis NCIMB 11871 catalyzes transferase reaction from β (1–2)-fructosyl to 2-OH of l-sugars (l-glucose, l-rhamnose, l-galactose, l-fucose, and l-xylose) [123]. Synthetic sucrose analogues (Man-Fru, Gal-Fru, Xyl-Fru, and Fuc-Fru) have also been tested as a substrate, and successful production of a wide range of hetero fructooligosacharides (Gal-(Fru)n-Fru (n > 12) Xyl-(Fru)n-Fru (n = 1–8) were achieved [130]. Recombinant levansucrase from Clostridium arbusti SL206 is able to synthesize sufficient amount of raffinose form sucrose and melibiose, a disaccharide of galactose and sucrose linked with α (1–6) glycosidic bond [171].
Structural and Functional Aspects of Fructansucrases (e.g., Levansucrase)
Levansucrase belongs to GH-68 family of glycosyl hydrolase. The levansucrase protein has three conserved regions with defined functions of (i) a signal peptide and N-terminal stretch with alteration in chain length; (ii) a conserved catalytic domain constituted of ~ 500 amino acids, characteristic of GH-68 family; and (iii) a C-terminal region with varied chain length [47] (Fig. 2).
-
1.
A signal peptide and N-terminal stretch: Mostly levansucrases are secreted extracellular due to the presence of a N-terminal signal peptide of different sizes such as of 37, 32, and 29 amino acids in levansucrase of Lactobacillus sanfranciscensis TMW 1.392, L. mesenteroids, and B. subtilis, respectively [169, 172] (Fig. 2). The cellular mechanism for extracellular secretion of proteins differs in gram-positive and gram-negative bacteria. Levansucrases in gram-positive bacteria (B. amyloliquefaciens, Streptococcus salivarius, Lactobacillus reuteri, L. mesenteroids, B. subtilis, etc.) are secreted by signal-peptide-dependent mechanism, while gram-negative bacteria (Gluconacetobacter xylinus, Erwinia amylovora, Acetobacter xylinum NCI 1005, and Zymomonas mobilis) follow the signal-peptide-independent mechanism [157, 173]. The extracellular secretion of levansucrase in a signal-peptide-dependent pathway is an exception in case of the gram-negative bacterium, Gluconacetobacter diazotrophicus [157]. Levansucrase of Lactobacillus sanfranciscens contains an unusual direct repeat of DNATSGSTKQESSIAN (16 × 7) adjacent to the signal peptide that does not show homology with other FTases [169]. Further, there is a stretch of hydrophobic amino acid next to the signal peptide, for which no function could be assigned so far; however, its deletion causes an increase in the enzyme activity [174].
-
2.
Catalytic domain: High-resolution crystal structure of levansucrase of B. subtilis (in ligand free as well as in substrate bound from at the resolution of 1.5 and 2.1 Å) revealed the presence of five-bladed β-propeller. This kind of fold was firstly observed in GH-43 family α-l-arabinanase A43 (Arb43A) of Cellvibrio japonicas [175, 176]. B. subtilis levansucrase showed the topology similar to other β-propellers, i.e., five sheets (I–V) folded in a manner forming a “W” shape with four antiparellel β-stands. Like levansucrase of B. subtilis, crystal structure of G. diazotrophicus shows a similar kind of five-bladed β-propeller-type structure, though it is a gram-negative bacteria [177]. The highly conserved motifs in the GH 68 family are VWD-86, EWSG-165, RDP-248, DEIER-343, and TYS-412, which contribute in cavity formation of propeller. In GH 32 family, glycoside hydrolase enzymes additionally contain EWSG-165 and RDP-248 as conserved motifs [176].
A hypothetical diagram showing the arrangement of domains in fructosyltransferase
The acidic amino acid residues, e.g., Asp and Glu, are mostly involved in synthesis of the central cavity in the catalytic domain of FTases and levensucrases. Mutation in Asp247 to Asn led to substantial decrease (75- to 3500-fold) in K cat values, while no significant change was observed in K m of levansucrase [177]. In Z. mobilis levansucrase, substitution of Glu 278 with Asp caused reduction in K cat value by 30-fold, but substitution with histidine led to drastically reduced enzyme activity [136]. Asp194 and Glu 278 are involved in acid base catalysis; carboxylate of Asp acts as nucleophile and attacks on the oxygen linked to C-1 of fructosyl, whereas the carboxyl group of Glu278 acts as a proton donor and consequently cleaves the β (1–2) bond, liberating glucose. Thus, fructose moiety, which is bound as intermediate to the enzyme, is transferred to C-2 or C-6 position of the fructose residue of another sucrose molecule [178]. Mutational studies on B. subtilis levansucrase revealed that Asp86 and Glu342 are essential for its catalytic activity. Asp247 is needed at the time of catalysis, but its direct role is not clear. Further, the residues involved in substrate binding and release of the product are not obvious [47]. In levansucrase of B. subtilis, Arg331 (His296 in Z. mobilis) are found crucial for executing polymerization reaction. The mutants (Arg331Lys, Arg331Ser, and Arg331Leu) in B. subtilis were unable to produce levan, but kestose was produced [155].
Generally, metal ions are not essential for the activity of levansucrases; however, presence of Ca2+ ion may give a positive impact on its activity. Levansucrase of S. salivarius showed 1.5-fold enhancement in the activity upon addition of 1 mM Ca2+ in the reaction [136]. The 3D structure analysis of B. subtilis levensucrase suggested a possible role of Asp339 residue in interaction with Ca2+ [176].
-
3.
C-terminal domain: In FTase, C-terminal domain is involved in substrate specificity and product size [47]. The C-terminal domain contains a cell-wall anchoring motif LPXTG, which helps in the attachment of the enzyme to the cell wall of the host organism. The signature sequence has been identified in levansucrase of S. salivarius ATCC 25975 l, inulosucrase, and levansucrase from L. reuteri 121 [176, 177].
Applications of Fructooligosaccharides
FOS is a well-known preferential carbon source for probiotics. It enhances growth of beneficial intestinal microbiota and impedes pathogenic organisms. Apart from bifidogenic effects, the regular and adequate intake of the non-digestible FOS gives beneficial effects in case of the problems associated with gastrointestinal disorders, obesity, diarrhea, osteoporosis, atherosclerotic, cardiovascular, and type 2 diabetes diseases [179]. FOS is recommended to the patients suffering from acute diarrhea, which is a common problem in children. FOS is known to stimulate the absorption of water and electrolyte in the gut mucosa [180, 181]. It has been investigated that the mixture of fructooligosaccharide and galactooligosaccharide is helpful in controlling the symptoms of phenylketonuria in infants [181]. Consumption of FOS reduces generation of genotoxins and β-glucuronidase enzyme that generate carcinogens in the intestine, and thus regulating incidences of colon cancer [2, 182]. FOS is also useful in controlling inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis disease [183]. Diarrhea is generally caused by Clostridium difficile. Consumption of FOS and inulin has been shown to lower the colonization of Clostridium sp. in the intestine, reducing the risk of diarrhea [4, 184].
In recent days, fructooligosaccharides have been emerged as a prebiotic functional food additive of GRAS (Generally Recognized As Safe) status. Use of inulin improves the quality of bread and skim milk. FOS has laxative property; therefore, nowadays it is included in formulae and food products for infants. Inulin and FOS are used to enhance free fatty acid profile of cheese. The taste profile of FOS is quite similar to sucrose, with ~ 30% less sweetness, higher water retention capacity and no cooling effect. Therefore, it is used in food products as low or no added sugars in formulations such as ice creams, dairy dessert, yogurts, and bakery products [185]. The fermentation of FOS in intestine generates short-chain fatty acids and other organic acids that decrease luminal pH, thereby enhancing the bioavailability of nutritionally important minerals [183, 186]. Increased calcium absorption, as a result of FOS intake, has been demonstrated, which potentially increases bone mineral density [187].
Future Prospects
Increasing trends in consumption of healthy foods containing non-digestible carbohydrates as health-promoting prebiotic ingredients have generated a huge market for oligosaccharides. This has created a demand of utilization of natural sources containing prebiotic oligosaccharides. As exploitation of natural resources for large-scale production of oligosaccharides is not affordable, the novel technologies for pilot production of these high-value functional biomolecules become crucial. Limited information is available on structural and functional attributes of enzymes useful in oligosaccharide synthesis. Efforts are needed to explore more about the mechanism of action and function of different domains and motifs of these enzymes. Limited knowledge about the relationship between structure and functional property of prebiotics is a barrier in preparation of the best possible mixture of oligosaccharides that can act as a potential prebiotic formulations. Genetic engineering approaches are to be employed for the development of efficient and stable biocatalysts leading to industrial production of prebiotic oligosaccharides. The technology development not only requires exploration of organisms expressing enzymes for oligosaccharide generation, enzyme engineering, and designing of engineered cellular factories for enzyme production and prebiotic molecule biosynthesis, but also the utilization of low-cost abundant biomass and agro-industrial residues for accelerated and economical production of prebiotic and functional molecules. Further, the challenge lies in the economical downstream processing and production of oligosaccharides with an acceptable level of purity.
References
Raman, M., Ambalam, P., & Doble, M. (2016). Bioactive carbohydrate: prebiotics and colorectal cancer. In probiotics and bioactive carbohydrates in colon cancer management. Springer India, 57–82.
Hutkins, R. W., Krumbeck, J. A., Bindels, L. B., Cani, P. D., Fahey, G., Goh, Y. J., Hamaker, B., Martens, E. C., Mills, D. A., Rastal, R. A., & Vaughan, E. (2016). Prebiotics: why definitions matter. Current Opinion in Biotechnology, 37, 1–7.
Younis, K., Ahmad, S., & Jahan, K. (2015). Health benefits and application of prebiotics in foods. Journal of Food Processing and Technology, 6(433), 2.
Rastall, R. A. (2010). Functional oligosaccharides: application and manufacture. Annual Review of Food Science and Technology, 1, 305–339.
Gibson, G. R., & Roberfroid, M. B. (1995). Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. The Journal of Nutrition, 125(6), 1401.
Vandenplas, Y., Zakharova, I., & Dmitrieva, Y. (2015). Oligosaccharides in infant formula: more evidence to validate the role of prebiotics. British Journal of Nutrition, 113(09), 1339–1344.
Bird, A., Conlon, M., Christophersen, C., & Topping, D. (2010). Resistant starch, large bowel fermentation and a broader perspective of prebiotics and probiotics. Beneficial Microbes, 1(4), 423–431.
Puertollano, E., Kolida, S., & Yaqoob, P. (2014). Biological significance of short-chain fatty acid metabolism by the intestinal microbiome. Current Opinion in Clinical Nutrition & Metabolic Care, 17(2), 139–144.
Ríos-Covián, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., & de los Reyes-Gavilán, C.G. & Salazar, N. (2016). Intestinal short chain fatty acids and their link with diet and human health. Frontiers in Microbiology, 7. https://doi.org/10.3389/fmicb.2016.00185.
Itaya, N. M., Asega, A. F., Carvalho, M. A. M., & Rita de Cássia, L. (2007). Hydrolase and fructosyltransferase activities implicated in the accumulation of different chain size fructans in three Asteraceae species. Plant Physiology and Biochemistry, 45(9), 647–656.
Sangeetha, P. T., Ramesh, M. N., & Prapulla, S. G. (2005). Recent trends in the microbial production, analysis and application of fructooligosaccharides. Trends in Food Science & Technology, 16(10), 442–457.
Voragen, A. G. (1998). Technological aspects of functional food-related carbohydrates. Trends in Food Science & Technology, 9(8), 328–335.
Prakash, M. D. (1984). Occurrence of glycoprotein glycosidases in mature seeds of mung bean (Vigna radiata). Phytochemistry, 23(2), 257–260.
Moure, A., Gullón, P., Domínguez, H., & Parajó, J. C. (2006). Advances in the manufacture, purification and applications of xylooligosaccharides as food additives and nutraceuticals. Process Biochemistry, 41(9), 1913–1923.
Intanon, M., Arreola, S. L., Pham, N. H., Kneifel, W., Haltrich, D., & Nguyen, T. H. (2014). Nature and biosynthesis of galactooligosaccharides related to oligosaccharides in human breast milk. FEMS Microbiology Letters, 353(2), 89–97.
Lina, B. A. R., Jonker, D., & Kozianowski, G. (2002). Isomaltulose (Palatinose®): A review of biological and toxicological studies. Food and Chemical Toxicology, 40(10), 1375–1381.
Holck, J., Hjernø, K., Lorentzen, A., Vigsnæs, L. K., Hemmingsen, L., Licht, T. R., Mikkelsen, J. D., & Meyer, A. S. (2011). Tailored enzymatic production of oligosaccharides from sugar beet pectin and evidence of differential effects of a single DP chain length difference on human faecal microbiota composition after in vitro fermentation. Process Biochemistry, 46(5), 1039–1049.
Kwon, H. J., Jeon, S. J., You, D. J., Kim, K. H., Jeong, Y. K., Kim, Y. H., Kim, Y. M., & Kim, B. W. (2003). Cloning and characterization of an exoinulinase from Bacillus polymyxa. Biotechnology Letters, 25(2), 155–159.
Rey, M. W., Ramaiya, P., Nelson, B. A., Brody-Karpin, S. D., Zaretsky, E. J., Tang, M., de Leon, A. L., Xiang, H., Gusti, V., Clausen, I. G., & Olsen, P. B. (2004). Complete genome sequence of the industrial bacterium Bacillus licheniformis and comparisons with closely related bacillus species. Genome Biology, 5(10), 77.
Schell, M. A., Karmirantzou, M., Snel, B., Vilanova, D., Berger, B., Pessi, G., Zwahlen, M. C., Desiere, F., Bork, P., Delley, M., & Pridmore, R. D. (2002). The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proceedings of the National Academy of Sciences, 99(22), 14422–14427.
Kim, K. Y., Koo, B. S., JO, D., & Kim, S. I. (2004). Cloning, expression, and purification of exoinulinase from Bacillus sp. snu-7. Journal of Microbiology and Biotechnology, 14(2), 344–349.
Tsujimoto, Y., Watanabe, A., Nakano, K., Watanabe, K., Matsui, H., Tsuji, K., Tsukihara, T., & Suzuki, Y. (2003). Gene cloning, expression, and crystallization of a thermostable exo-inulinase from Geobacillus stearothermophilus KP1289. Applied Microbiology and Biotechnology, 62(2–3), 180–185.
Barranco-Florido, E., Garcia-Garibay, M., Gómez-Ruiz, L., & Azaola, A. (2001). Immobilization system of Kluyveromyces marxianus cells in barium alginate for inulin hydrolysis. Process Biochemistry, 37(5), 513–519.
Moriyama, S., Tanaka, H., Uwataki, M., Muguruma, M., & Ohta, K. (2003). Molecular cloning and characterization of an exoinulinase gene from Aspergillus niger strain 12 and its expression in Pichia pastoris. Journal of Bioscience and Bioengineering, 96(4), 324–331.
Young-man, K., Kim, H. Y., & Choi, Y. J. (2000). Cloning and characterization of Pseudomonas mucidolens exoinulinase. Journal of Microbiology and Biotechnology, 10(2), 238–243.
Liebl, W., Brem, D., & Gotschlich, A. (1998). Analysis of the gene for β-fructosidase (invertase, inulinase) of the hyperthermophilic bacterium Thermotoga maritima, and characterisation of the enzyme expressed in Escherichia coli. Applied Microbiology and Biotechnology, 50(1), 55–64.
Arand, M., Golubev, A. M., Neto, J. B., Polikarpov, I., Wattiez, R., Korneeva, O. S., Eneyskaya, E. V., Kulminskaya, A. A., Shabalin, K. A., Shishliannikov, S. M., & Chepurnaya, O. V. (2002). Purification, characterization, gene cloning and preliminary X-ray data of the exo-inulinase from Aspergillus awamori. Biochemical Journal, 362(1), 131–135.
Uhm, T. B., Chae, K. S., Lee, D. W., Kim, H. S., Cassart, J. P., & Vandenhaute, J. (1998). Cloning and nucleotide sequence of the endoinulinase-encoding gene, inu2, from Aspergillus ficuum. Biotechnology Letters, 20(8), 809–812.
Kang, S. I., Chang, Y. J., Oh, S. J., & Kim, S. I. (1998). Purification and properties of an endo-inulinase from an Arthrobacter sp. Biotechnology Letters, 20(10), 983–986.
Ohta, K., Akimoto, H., Matsuda, S., Toshimitsu, D., & Nakamura, T. (1998). Molecular cloning and sequence analysis of two endoinulinase genes from Aspergillus niger. Bioscience, Biotechnology, and Biochemistry, 62(9), 1731–1738.
Akimoto, H., Kiyota, N., Kushima, T., & Nakamura, T. (2000). Molecular cloning and sequence analysis of an endoinulinase gene from Penicillium sp. strain TN-88. Bioscience, Biotechnology, and Biochemistry, 64(11), 2328–2335.
Onodera, S., Murakami, T., Ito, H., Mori, H., Matsui, H., Honma, M., Chiba, S., & Shiomi, N. (1996). Molecular cloning and nucleotide sequences of cDNA and gene encoding endo-inulinase from Penicillium purpurogenum. Bioscience, Biotechnology, and Biochemistry, 60(11), 1780–1785.
Slavin, J. (2013). Fiber and prebiotics: mechanisms and health benefits. Nutrients, 5, 1417–1435.
Biedrzycka, E., & Bielecka, M. (2004). Prebiotic effectiveness of fructans of different degrees of polymerization. Trends in Food Science & Technology, 15(3), 170–175.
Vera, C., Córdova, A., Aburto, C., Guerrero, C., Suárez, S., & Illanes, A. (2016). Synthesis and purification of galactooligosaccharides: state of the art. World Journal of Microbiology and Biotechnology, 32(12), 197.
Monteagudo-Mera, A., Arthur, J. C., Jobin, C., Keku, T., Bruno-Barcena, J. M., & Azcarate-Peril, M. A. (2016). High purity galactooligosaccharides enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome. Beneficial Microbes, 7(2), 247–264.
Bhatia, S., Prabhu, P. N., Benefiel, A. C., Miller, M. J., Chow, J., Davis, S. R., & Gaskins, H. R. (2015). Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. Molecular Nutrition & Food Research, 59(3), 566–573.
Fanaro, S., Boehm, G., Garssen, J., Knol, J., Mosca, F., Stahl, B., & Vigi, V. (2005). Galacto-oligosaccharides and long-chain fructo-oligosaccharides as prebiotics in infant formulas: a review. Acta Paediatrica, 94(s449), 22–26.
Nabarlatz, D., Ebringerová, A., & Montané, D. (2007). Autohydrolysis of agricultural by-products for the production of xylooligosaccharides. Carbohydrate Polymers, 69(1), 20–28.
Al-Sheraji, S. H., Ismail, A., Manap, M. Y., Mustafa, S., Yusof, R. M., & Hassan, F. A. (2013). Prebiotics as functional foods: a review. Journal of Functional Foods, 5(4), 1542–1553.
Crittenden, R. G., & Playne, M. (1996). Production, properties and applications of food-grade oligosaccharides. Trends in Food Science & Technology, 7(11), 353–361.
Niu, D., Qiao, J., Li, P., Tian, K., Liu, X., Singh, S., & Lu, F. (2017). Highly efficient enzymatic preparation of isomaltooligosaccharides from starch using an enzyme cocktail. Electronic Journal of Biotechnology, 26, 46–51.
Basu, A., Mutturi, S., & Prapulla, S. G. (2016). Production of isomaltooligosaccharides (IMO) using simultaneous saccharification and transglucosylation from starch and sustainable sources. Process Biochemistry, 51(10), 1464–1471.
Kuriki, T., Yanase, M., Takata, H., Takesada, Y., Imanaka, T., & Okada, S. (1993). A new way of producing isomaltooligosaccharide syrup by using the transglycosylation reaction of neopullulanase. Applied and Environmental Microbiology, 59(4), 953–959.
Sharma, M., Patel, S. N., Lata, K., Singh, U., Krishania, M., Sangwan, R. S., & Singh, S. P. (2016). A novel approach of integrated bioprocessing of cane molasses for production of prebiotic and functional bioproducts. Bioresource Technology, 219, 311–318.
Iliev, I., Vassileva, T., Ignatova, C., Ivanova, I., Haertle, T., Monsan, P., & Chobert, J. M. (2008). Gluco-oligosaccharides synthesized by glucosyltransferases from constitutive mutants of Leuconostoc mesenteroides strain Lm 28. Journal of Applied Microbiology, 104(1), 243–250.
Van Hijum, S. A., Kralj, S., Ozimek, L. K., Dijkhuizen, L., & van Geel-Schutten, I. G. (2006). Structure-function relationships of glucansucrase and fructansucrase enzymes from lactic acid bacteria. Microbiology and Molecular Biology Reviews, 70(1), 157–176.
Robyt, J. F., Yoon, S. H., & Mukerjea, R. (2008). Dextransucrase and the mechanism for dextran biosynthesis. Carbohydrate Research, 343(18), 3039–3048.
Kubik, C., Sikora, B., & Bielecki, S. (2004). Immobilization of dextransucrase and its use with soluble dextranase for glucooligosaccharides synthesis. Enzyme and Microbial Technology, 34(6), 555–560.
Goulas, A. K., Cooper, J. M., Grandison, A. S., & Rastall, R. A. (2004). Synthesis of isomaltooligosaccharides and oligodextrans in a recycle membrane bioreactor by the combined use of dextransucrase and dextranase. Biotechnology and Bioengineering, 88(6), 778–787.
Mussatto, S. I., & Mancilha, I. M. (2007). Non-digestible oligosaccharides: a review. Carbohydrate Polymers, 68(3), 587–597.
Fujimoto, Y., Hattori, T., Uno, S., Murata, T., & Usui, T. (2009). Enzymatic synthesis of gentiooligosaccharides by transglycosylation with β-glycosidases from Penicillium multicolor. Carbohydrate Research, 344(8), 972–978.
Kothari, D., & Goyal, A. (2015). Gentiooligosaccharides from Leuconostoc mesenteroides NRRL B-1426 dextransucrase as prebiotics and as a supplement for functional foods with anti-cancer properties. Food & Function, 6(2), 604–611.
Nanjo, F., Usui, T., & SUZKI, T. (1984). Mode of action of an exo-β-(1→ 3)-D-glucanase on the laminaran from Eisenia bicyclis. Agricultural and biological chemistry., 48(6), 1523–1532.
Bouhnik, Y., Raskine, L., Simoneau, G., Vicaut, E., Neut, C., Flourié, B., Brouns, F., & Bornet, F. R. (2004). The capacity of nondigestible carbohydrates to stimulate fecal Bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study. The American Journal of Clinical Nutrition, 80(6), 1658–1664.
Nurhayati, Y., Manaf, A. A., Osman, H., Abdullah, A. B. C., & Tang, J. Y. H. (2016). Effect of chitosan oligosaccharides on the growth of bifidobacterium species. Malaysian Journal of Applied Sciences, 1(1), 13–23.
Zou, P., Yang, X., Wang, J., Li, Y., Yu, H., Zhang, Y., & Liu, G. (2016). Advances in characterisation and biological activities of chitosan and chitosan oligosaccharides. Food Chemistry, 190, 1174–1181.
Muñoz-Almagro, N., Montilla, A., Moreno, F. J., & Villamiel, M. (2017). Modification of citrus and apple pectin by power ultrasound: effects of acid and enzymatic treatment. Ultrasonics Sonochemistry, 38, 807–819.
Gómez, B., Gullón, B., Yáñez, R., Schols, H., & Alonso, J. L. (2016). Prebiotic potential of pectins and pectic oligosaccharides derived from lemon peel wastes and sugar beet pulp: a comparative evaluation. Journal of Functional Foods, 20, 108–121.
Gómez, B., Yáñez, R., Parajó, J. C., & Alonso, J. L. (2016). Production of pectin-derived oligosaccharides from lemon peels by extraction, enzymatic hydrolysis and membrane filtration. Journal of Chemical Technology and Biotechnology, 91(1), 234–247.
Holck, J., Lorentzen, A., Vigsnæs, L. K., Licht, T. R., Mikkelsen, J. D., & Meyer, A. S. (2011). Feruloylated and nonferuloylated arabinooligosaccharides from sugar beet pectin selectively stimulate the growth of Bifidobacterium spp. in human fecal in vitro fermentations. Journal of Agricultural and Food Chemistry, 59(12), 6511–6519.
Margolles, A., & Clara, G. (2003). Purification and functional characterization of a novel α-l-arabinofuranosidase from Bifidobacterium longum B667. Applied and Environmental Microbiology, 69(9), 5096–5103.
Sulek, K., Vigsnaes, L. K., Schmidt, L. R., Holck, J., Frandsen, H. L., Smedsgaard, J., Skov, T. H., Meyer, A. S., & Licht, T. R. (2014). A combined metabolomic and phylogenetic study reveals putatively prebiotic effects of high molecular weight arabinooligosaccharides when assessed by in vitro fermentation in bacterial communities derived from humans. Anaerobe, 28, 68–77.
Rastall, R. A., & Maitin, V. (2002). Prebiotics and synbiotics: towards the next generation. Current Opinion in Biotechnology, 13(5), 490–496.
Hu, B., Gong, Q., Wang, Y., Ma, Y., Li, J., & Yu, W. (2006). Prebiotic effects of neoagarooligosaccharides prepared by enzymatic hydrolysis of agarose. Anaerobe, 12(5), 260–266.
Li, M., Li, G., Zhu, L., Yin, Y., Zhao, X., Xiang, C., Yu, G., & Wang, X. (2014). Isolation and characterization of an agarooligosaccharide (AO)-hydrolyzing bacterium from the gut microflora of Chinese individuals. PloS One, 9(3), e91106.
Qiu, D., Vuong, T., Valliyodan, B., Shi, H., Guo, B., Shannon, J. G., & Nguyen, H. T. (2015). Identification and characterization of a stachyose synthase gene controlling reduced stachyose content in soybean. Theoretical and Applied Genetics, 128(11), 2167–2176.
Song, Y. S., Lee, H. U., Park, C., & Kim, S. W. (2013). Optimization of lactulose synthesis from whey lactose by immobilized β-galactosidase and glucose isomerase. Carbohydrate Research, 369, 1–5.
Silveira, M. F., Masson, L. M. P., Martins, J. F. P., Álvares, T. D. S., Paschoalin, V. M. F., Lázaro de la Torre, C. & Conte-Junior, C. A. (2015). Simultaneous determination of lactulose and lactose in conserved milk by HPLC-RID. Journal of Chemistry, 2015(2015), 1–6.
Duarte, L. S., da Natividade Schöffer, J., Lorenzoni, A. S. G., Rodrigues, R. C., Rodrigues, E. & Hertz, P. F. (2017). A new bioprocess for the production of prebiotic lactosucrose by an immobilized β-galactosidase. Process Biochemistry, 55, 96–103.
Mu, W., Chen, Q., Wang, X., Zhang, T., & Jiang, B. (2013). Current studies on physiological functions and biological production of lactosucrose. Applied Microbiology and Biotechnology, 97(16), 7073–7080.
Bali, V., Panesar, P. S., Bera, M. B., & Panesar, R. (2015). Fructooligosaccharides: production, purification and potential applications. Critical Reviews in Food Science and Nutrition, 55(11), 1475–1490.
Casci, T., & Rastall, R. A. (2006). Manufacture of prebiotic oligosaccharides (pp. 29–55). Prebiotics: Development and applications, New York, John Wiley.
Campbell, J. M., Bauer, L. L., Fahey, G. C., Hogarth, A. J. C. L., Wolf, B. W., & Hunter, D. E. (1997). Selected fructooligosaccharide (1-kestose, nystose, and 1F-β-fructofuranosylnystose) composition of foods and feeds. Journal of Agricultural and Food Chemistry, 45(8), 3076–3082.
Montet, D., & Ray, R. C. (2016). Fermented foods. Biochemistry and biotechnology. New York, NY: CRC Press.
Wang, J., Sporns, P., & Low, N. H. (1999). Analysis of food oligosaccharides using MALDI-MS: quantification of fructooligosaccharides. Journal of Agricultural and Food Chemistry, 47(4), 1549–1557.
Roberfroid, M., & Slavin, J. (2000). Nondigestible oligosaccharides. Critical Reviews in Food Science and Nutrition, 40(6), 461–480.
Bornet, F. R. J. (1994). Undigestible sugars in food products. The American Journal of Clinical Nutrition, 59(3), 763–769.
Linde, D., Rodríguez-Colinas, B., Estévez, M., Poveda, A., Plou, F. J., & Lobato, M. F. (2012). Analysis of neofructooligosaccharides production mediated by the extracellular β-fructofuranosidase from Xanthophyllomyces dendrorhous. Bioresource Technology, 109, 123–130.
Kilian, S., Kritzinger, S., Rycroft, C., Gibson, G., & Du Preez, J. (2002). The effects of the novel bifidogenic trisaccharide, neokestose, on the human colonic microbiota. World Journal of Microbiology and Biotechnology, 18(7), 637–644.
Trujillo, L. E., Arrieta, J. G., Dafhnis, F., Garcıa, J., Valdes, J., Tambara, Y., & Hernández, L. (2001). Fructooligosaccharides production by the Gluconacetobacter diazotrophicus levansucrase expressed in the methylotrophic yeast Pichia pastoris. Enzyme and Microbial Technology, 28(2), 139–144.
Bhatia, I. S., & Nandra, K. S. (1979). Studies on fructosyl transferase from Agave americana. Phytochemistry, 18(6), 923–927.
Mellado-Mojica, E., de la Vara, L. E. G., & López, M. G. (2016). Fructan active enzymes (FAZY) activities and biosynthesis of fructooligosaccharides in the vacuoles of Agave tequilana Weber Blue variety plants of different age. Planta, 245(2), 265–281.
Bhatia, I. S., Satyanarayana, M. N., & Srinivasan, M. (1955). Transfructosidase from Agave vera cruz Mill. Biochemical Journal, 61(1), 171.
Henry, R. J., & Darbyshire, B. (1980). Sucrose: Sucrose fructosyltransferase and fructan: Fructan fructosyltransferase from Allium cepa. Phytochemistry, 19(6), 1017–1020.
Verhaest, M., Le Roy, K., Sansen, S., De Coninck, B., Lammens, W., De Ranter, C. J., Van Laere, A., Van den Ende, W., & Rabijns, A. (2005). Crystallization and preliminary X-ray diffraction study of a cell-wall invertase from Arabidopsis thaliana. Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 61(8), 766–768.
Shiomi, N. (1982). Purification and characterisation of 1F-fructosyltransferase from the roots of asparagus (Asparagus officinalis L.) Carbohydrate Research, 99(2), 157–169.
Lüscher, M., Hochstrasser, U., Boller, T., & Wiemken, A. (2000). Isolation of sucrose: sucrose 1-fructosyltransferase (1-SST) from barley (Hordeum vulgare). New Phytologist, 145(2), 225–232.
Singh, R., & Bhatia, I. S. (1971). Isolation and characterization of fructosyltransferase from chicory roots. Phytochemistry, 10(3), 495–502.
Edelman, J., & Jeeeord, T. G. (1968). The mechanisim of fructosan metabolism in higher plants as exemplified in Helianthus tuberosus. New Phytologist, 67(3), 517–531.
Chandorkar, K. R., & Collins, F. W. (1972). De novo synthesis of fructooligosaccharides in leaf disks of certain Asteraceae. Canadian Journal of Botany, 50(2), 295–303.
Abeynayake, S. W., Byrne, S., Nagy, I., Jonavičienė, K., Etzerodt, T. P., Boelt, B., & Asp, T. (2015). Changes in Lolium perenne transcriptome during cold acclimation in two genotypes adapted to different climatic conditions. BMC Plant Biology, 15(1), 250.
Nagamatsu, Y., Yahata, M., Fukada, T., & Hatanaka, C. (1990). Identification of 1-kestose and neokestose based oligofruetans in Lycoris radiata herb tissues. Agricultural and Biological Chemistry, 54(5), 1291–1292.
Tamura, K. I., Sanada, Y., Tase, K., & Yoshida, M. (2014). Fructan metabolism and expression of genes coding fructan metabolic enzymes during cold acclimation and overwintering in timothy (Phleum pratense). Journal of Plant Physiology, 171(11), 951–958.
Barreteau, H., Delattre, C., & Michaud, P. (2006). Production of oligosaccharides as promising new food additive generation. Food Technology and Biotechnology, 44(3), 323.
Jiang, H., Ma, Y., Chi, Z., Liu, G. L., & Chi, Z. M. (2016). Production, purification, and gene cloning of a β-fructofuranosidase with a high inulin-hydrolyzing activity produced by a novel yeast Aureobasidium sp. P6 isolated from a mangrove ecosystem. Marine Biotechnology, 18(4), 500–510.
Ghazi, I., Fernandez-Arrojo, L., Garcia-Arellano, H., Ferrer, M., Ballesteros, A., & Plou, F. J. (2007). Purification and kinetic characterization of a fructosyltransferase from Aspergillus aculeatus. Journal of Biotechnology, 128(1), 204–211.
Ganaie, M. A., Gupta, U. S., & Kango, N. (2013). Screening of biocatalysts for transformation of sucrose to fructooligosaccharides. Journal of Molecular Catalysis B: Enzymatic, 97, 12–17.
Hang, Y. D., Woodams, E. E., & Jang, K. Y. (1995). Enzymatic conversion of sucrose to kestose by fungal extracellular fructosyltransferase. Biotechnology Letters, 17(3), 295–298.
Chen, W. C., & Liu, C. H. (1996). Production of β-fructofuranosidase by Aspergillus japonicus. Enzyme and Microbial Technology, 18(2), 153–160.
L’Hocine, L., Wang, Z., Jiang, B., & Xu, S. (2000). Purification and partial characterization of fructosyltransferase and invertase from Aspergillus niger AS0023. Journal of Biotechnology, 81(1), 73–84.
Murakami, H., Muroi, H., Kuramoto, T., Tamura, Y., Mizutani, K., Nakano, H., & Kitahata, S. (1990). Purification and some properties of a levanase from Streptomyces sp. no. 7–3. Agricultural and Biological Chemistry, 54(9), 2247–2255.
Van Balken, J. A. M., Van Dooren, T. J., Van den Tweel, W. J. J., Kamphuis, J., & Meijer, E. M. (1991). Production of 1-kestose with intact mycelium of Aspergillus phoenicis containing sucrose-1F-fructosyltransferase. Applied Microbiology and Biotechnology, 35(2), 216–221.
Muramatsu, M., & Nakakuki, T. (1995). Enzymatic synthesis of novel fructosyl and oligofructosyl trehaloses by Aspergillus sydowi β-fructofuranosidase. Bioscience, Biotechnology, and Biochemistry, 59(2), 208–212.
Yun, J. W., Kim, D. H., & Song, S. K. (1997). Enhanced production of fructosyltransferase and glucosyltransferase by substrate-feeding cultures of Aureobasidium pullulans. Journal of Fermentation and Bioengineering, 84(3), 261–263.
Lim, J. S., Park, M. C., Lee, J. H., Park, S. W., & Kim, S. W. (2005). Optimization of culture medium and conditions for neo-fructooligosaccharides production by Penicillium citrinum. European Food Research and Technology, 221(5), 639–644.
Dhake, A. B., & Patil, M. B. (2007). Effect of substrate feeding on production of fructosyltransferase by Penicillium purpurogenum. Brazilian Journal of Microbiology, 38(2), 194–199.
Barthomeuf, C., & Pourrat, H. (1995). Production of high-content fructooligosaccharides by an enzymatic system from Penicillium rugulosum. Biotechnology Letters, 17(9), 911–916.
Hernalsteens, S., & Maugeri, F. (2010). Synthesis of fructooligosaccharides using extracellular enzymes from Rhodotorula sp. Journal of Food Biochemistry, 34(3), 520–534.
Linde, D., Macias, I., Fernández-Arrojo, L., Plou, F. J., Jiménez, A., & Fernández-Lobato, M. (2009). Molecular and biochemical characterization of a β-fructofuranosidase from Xanthophyllomyces dendrorhous. Applied and Environmental Microbiology, 75(4), 1065–1073.
Bergeron, L. J., Morou-Bermudez, E., & Burne, R. A. (2000). Characterization of the fructosyltransferase gene of Actinomyces naeslundii WVU45. Journal of Bacteriology, 182(13), 3649–3654.
Pabst, M. J. (1977). Levan and levansucrase of Actinomyces viscosus. Infection and Immunity, 15(2), 518–526.
Tonozuka, T., Tamaki, A., Yokoi, G., Miyazaki, T., Ichikawa, M., Nishikawa, A., & Ito, T. (2012). Crystal structure of a lactosucrose-producing enzyme, Arthrobacter sp. K-1 β-fructofuranosidase. Enzyme and Microbial Technology, 51(6), 359–365.
Olivares-Illana, V., López-Munguía, A., & Olvera, C. (2003). Molecular characterization of inulosucrase from Leuconostoc citreum: a fructosyltransferase within a glucosyltransferase. Journal of Bacteriology, 185(12), 3606–3612.
Woo Kim, B., Won Choi, J., & Won Yun, J. (1998). Selective production of GF4-fructooligosaccharide from sucrose by a new transfructosylating enzyme. Biotechnology Letters, 20(11), 1031–1034.
Korneli, C., Biedendieck, R., David, F., Jahn, D., & Wittmann, C. (2013). High yield production of extracellular recombinant levansucrase by Bacillus megaterium. Applied Microbiology and Biotechnology, 97(8), 3343–3353.
Zhang, T., Li, R., Qian, H., Mu, W., Miao, M., & Jiang, B. (2014). Biosynthesis of levan by levansucrase from Bacillus methylotrophicus SK 21.002. Carbohydrate Polymers, 101, 975–981.
Gay, P., Chalumeau, H., & Steinmetz, M. (1983). Chromosomal localization of gut, fruC, and pfk mutations affecting genes involved in Bacillus subtilis D-glucitol catabolism. Journal of Bacteriology, 153(3), 1133–1137.
Vaidya, V. D., & Prasad, D. T. (2012). Thermostable levansucrase from Bacillus subtilis BB04, an isolate of banana peel. Journal of Biochemical Technology, 3(4), 322–327.
Abdel-Fattah, A. F., Mahmoud, D. A., & Esawy, M. A. (2005). Production of levansucrase from Bacillus subtilis NRC 33a and enzymic synthesis of levan and fructooligosaccharides. Current Microbiology, 51(6), 402–407.
Liu, Q., Yu, S., Zhang, T., Jiang, B., & Mu, W. (2017). Efficient biosynthesis of levan from sucrose by a novel levansucrase from Brenneria goodwinii. Carbohydrate Polymers, 157, 1732–1740.
Looten, P., Blanchet, D., & Vandecasteele, J. P. (1987). The β-fructofuranosidase activities of a strain of Clostridium acetobutylicum grown on inulin. Applied Microbiology and Biotechnology, 25(5), 419–425.
Seibel, J., Moraru, R., Götze, S., Buchholz, K., Na’amnieh, S., Pawlowski, A., & Hecht, H. J. (2006). Synthesis of sucrose analogues and the mechanism of action of Bacillus subtilis fructosyltransferase (levansucrase). Carbohydrate Research, 341(14), 2335–2349.
Gross, M., Geier, G., Rudolph, K., & Geider, K. (1992). Levan and levansucrase synthesized by the fireblight pathogen Erwinia amylovora. Physiological and Molecular Plant Pathology, 40(6), 371–381.
Chambert, R., & Petit-Glatron, M. F. (1991). Polymerase and hydrolase activities of Bacillus subtilis levansucrase can be separately modulated by site-directed mutagenesis. Biochemical Journal, 279(1), 35–41.
Tieking, M., Korakli, M., Ehrmann, M. A., Gänzle, M. G., & Vogel, R. F. (2003). In situ production of exopolysaccharides during sourdough fermentation by cereal and intestinal isolates of lactic acid bacteria. Applied and Environmental Microbiology, 69(2), 945–952.
Waldherr, F. W., Meissner, D., & Vogel, R. F. (2008). Genetic and functional characterization of Lactobacillus panis levansucrase. Archives of Microbiology, 190(4), 497.
Van Hijum, S. A. F. T., Szalowska, E., Van Der Maarel, M. J. E. C., & Dijkhuizen, L. (2004). Biochemical and molecular characterization of a levansucrase from Lactobacillus reuteri. Microbiology, 150(3), 621–630.
Han, J., Xu, X., Gao, C., Liu, Z., & Wu, Z. (2016). Levan-producing Leuconostoc citreum strain BD1707 and its growth in tomato juice supplemented with sucrose. Applied and Environmental Microbiology, 82(5), 1383–1390.
Beine, R., Moraru, R., Nimtz, M., Na’amnieh, S., Pawlowski, A., Buchholz, K., & Seibel, J. (2008). Synthesis of novel fructooligosaccharides by substrate and enzyme engineering. Journal of Biotechnology, 138(1), 33–41.
Xu, X., Gao, C., Liu, Z., Wu, J., Han, J., Yan, M., & Wu, Z. (2016). Characterization of the levan produced by Paenibacillus bovis sp. nov BD3526 and its immunological activity. Carbohydrate Polymers, 144, 178–186.
Youssef, G. A., Youssef, A. S., Talha, S., & El-Aassar, S. A. (2014). Increased fructosyltranseferase (levansucrase) production by optimizing culture condition from Pediococcus acidilactici strain in shaking batch cultures. Life Science Journal, 11(7), 33–47.
Hettwer, U., Gross, M., & Rudolph, K. (1995). Purification and characterization of an extracellular levansucrase from Pseudomonas syringae pv. Phaseolicola. Journal of Bacteriology, 177(10), 2834–2839.
Ohtsuka, K., Hino, S., Fukushima, T., Ozawa, O., Kanematsu, T., & Uchida, T. (1992). Characterization of levansucrase from Rahnella aquatilis JCM-1683. Bioscience, Biotechnology, and Biochemistry, 56(9), 1373–1377.
Schroeder, V. A., Michalek, S. M., & Macrina, F. L. (1989). Biochemical characterization and evaluation of virulence of a fructosyltransferase-deficient mutant of Streptococcus mutans V403. Infection and Immunity, 57(11), 3560–3569.
Song, D. D., & Jacques, N. A. (1999). Mutation of aspartic acid residues in the fructosyltrans- ferase of Streptococcus salivarius ATCC 25975. Biochemical Journal, 344(1), 259–264.
Bekers, M., Laukevics, J., Upite, D., Kaminska, E., Vigants, A., Viesturs, U., Pankova, L., & Danilevics, A. (2002). Fructooligosaccharide and levan producing activity of Zymomonas mobilis extracellular levansucrase. Process Biochemistry, 38(5), 701–706.
Antosova, M., & Polakovic, M. (2002). Fructosyltransferases: the enzymes catalyzing production of fructooligosaccharides. Chemical papers-slovak Academy of Sciences, 55(6), 350–358.
Fernandez, R. C., Ottoni, C. A., Da Silva, E. S., Matsubara, R. M. S., Carter, J. M., Magossi, L. R., Wada, M. A. A., de Andrade Rodrigues, M. F., Maresma, B. G., & Maiorano, A. E. (2007). Screening of β-fructofuranosidase-producing microorganisms and effect of pH and temperature on enzymatic rate. Applied Microbiology and Biotechnology, 75(1), 87–93.
Hendry, G. A. (1993). Evolutionary origins and natural functions of fructans - a climatological, biogeographic and mechanistic appraisal. New Phytologist, 123(1), 3–14.
Livingston, D. P., Hincha, D. K., & Heyer, A. G. (2009). Fructan and its relationship to abiotic stress tolerance in plants. Cellular and Molecular Life Sciences, 66(13), 2007–2023.
van Arkel, J., Sévenier, R., Hakkert, J. C., Bouwmeester, H. J., Koops, A. J., & van der Meer, I. M. (2013). Tailor-made fructan synthesis in plants: a review. Carbohydrate. Polymer., 93, 48–56.
Koops, A. J., & Jonker, H. H. (1994). Purification and characterization of the enzymes of fructan biosynthesis in tubers of Helianthus tuberosus ‘Colombia’I. Fructan: fructan fructosyl transferase. Journal of Experimental Botany, 45(11), 1623–1631.
Ende, W. V., Michiels, A., Roover, J. D., & Laere, A. (2002). Fructan biosynthetic and breakdown enzymes in dicots evolved from different invertases. Expression of fructan genes throughout chicory development. The Scientific World Journal, 2, 1281–1295.
Altenbach, D., Nüesch, E., Meyer, A. D., Boller, T., & Wiemken, A. (2004). The large subunit determines catalytic specificity of barley sucrose: fructan 6-fructosyltransferase and fescue sucrose: sucrose 1-fructosyltransferase. FEBS Letters, 567(2–3), 214–218.
Eggleston, G., & Cote, G. L. (2003). Oligosaccharides in food and agriculture. ACS Symposium Series, 849. Chapter, 1, 1–14. https://doi.org/10.1021/bk-2003-0849.ch001.
Fujishima, M., Sakai, H., Ueno, K., Takahashi, N., Onodera, S., Benkeblia, N., & Shiomi, N. (2005). Purification and characterization of a fructosyltransferase from onion bulbs and its key role in the synthesis of fructo-oligosaccharides in vivo. New Phytologist, 165(2), 513–524.
Yesilirmak, F. & Sayers, Z. (2009). Heterelogous expression of plant genes. International Journal of Plant Genomics, 2009, doi.org/10.1155/2009/296482.
Frommer, W. B., & Ninnemann, O. (1995). Heterologous expression of genes in bacterial, fungal, animal, and plant cells. Annual Review of Plant Biology, 46(1), 419–444.
Dake, M. S., & Kumar, G. (2012). Partial purification and characterization of fructosyltransferase from Aureobasidium pullulans. International Journal of Science, Environment and Technology, 1(2), 88–98.
Seo, E. S., Lee, J. H., Cho, J. Y., Seo, M. Y., Lee, H. S., Chang, S. S., Lee, H. J., Choi, J. S., & Kim, D. (2004). Synthesis and characterization of fructooligosaccharides using levansucrase with a high concentration of sucrose. Biotechnology and Bioprocess Engineering, 9(5), 339–344.
Olvera, C., Centeno-Leija, S., & López-Munguía, A. (2007). Structural and functional features of fructansucrases present in Leuconostoc mesenteroides ATCC 8293. Antonie Van Leeuwenhoek, 92(1), 11–20.
Díez-Municio, M., de las Rivas, B., Jimeno, M. L., Muñoz, R., Moreno, F. J., & Herrero, M. (2013). Enzymatic synthesis and characterization of fructooligosaccharides and novel maltosylfructosides by inulosucrase from Lactobacillus gasseri DSM 20604. Applied and Environmental Microbiology, 79(13), 4129–4140.
Maugeri, F., & Hernalsteens, S. (2007). Screening of yeast strains for transfructosylating activity. Journal of Molecular Catalysis B: Enzymatic, 49(1), 43–49.
Steinmetz, M., Le Coq, D., Aymerich, S., Gonzy-Tréboul, G., & Gay, P. (1985). The DNA sequence of the gene for the secreted Bacillus subtilis enzyme levansucrase and its genetic control sites. Molecular and General Genetics, 200(2), 220–228.
Geier, G., & Geider, K. (1993). Characterization and influence on virulence of the levansucrase gene from the fireblight pathogen Erwinia amylovora. Physiological and Molecular Plant Pathology, 42(6), 387–404.
Arrieta, J., Hernandez, L., Coego, A., Suárez, V., Balmori, E., Menéndez, C., Petit-Glatron, M. F., Chambert, R., & Selman-Housein, G. (1996). Molecular characterization of the levansucrase gene from the endophytic sugarcane bacterium Acetobacter diazotrophicus SRT4. Microbiology, 142(5), 1077–1085.
Tian, F., Inthanavong, L., & Karboune, S. (2011). Purification and characterization of levansucrases from Bacillus amyloliquefaciens in intra-and extracellular forms useful for the synthesis of levan and fructooligosaccharides. Bioscience, Biotechnology, and Biochemistry, 75(10), 1929–1938.
Anwar, M. A., Kralj, S., van der Maarel, M. J., & Dijkhuizen, L. (2008). The probiotic Lactobacillus johnsonii NCC 533 produces high-molecular-mass inulin from sucrose by using an inulosucrase enzyme. Applied and Environmental Microbiology, 74(11), 3426–3433.
Jong, W. Y., & Seung, K. S. (1993). The production of high-content fructooligosaccharides from sucrose by the mixed-enzyme system of fructosyltransferase and glucose oxidase. Biotechnology Letters, 15(6), 573–576.
Dominguez, A. L., Rodrigues, L. R., Lima, N. M., & Teixeira, J. A. (2014). An overview of the recent developments on fructooligosaccharide production and applications. Food and Bioprocess Technology, 7(2), 324–337.
Wanker, E., Huber, A., & Schwab, H. (1995). Purification and characterization of the Bacillus subtilis levanase produced in Escherichia coli. Applied and Environmental Microbiology, 61(5), 1953–1958.
Chaudhary, A., Gupta, L. K., Gupta, J. K., & Banerjee, U. C. (1996). Purification and properties of levanase from Rhodotorula sp. Journal of Biotechnology, 46(1), 55–61.
Takahashi, N., Mizuno, F., & Takamori, K. (1983). Isolation and properties of levanase from Streptococcus salivarius KTA-19. Infection and Immunity, 42(1), 231–236.
Menéndez, C., Hernández, L., Selman, G., Mendoza, M. F., Hevia, P., Sotolongo, M., & Arrieta, J. G. (2002). Molecular cloning and expression in Escherichia coli of an exo-levanase gene from the endophytic bacterium Gluconacetobacter diazotrophicus SRT4. Current Microbiology, 45(1), 5–12.
Jensen, S. L., Diemer, M. B., Lundmark, M., Larsen, F. H., Blennow, A., Mogensen, H. K., & Nielsen, T. H. (2016). Levanase from Bacillus subtilis hydrolyses β-2, 6 fructosyl bonds in bacterial levans and in grass fructans. International Journal of Biological Macromolecules, 85, 514–521.
Silva, M. F., Rigo, D., Mossi, V., Golunski, S., de Oliveira Kuhn, G., Di Luccio, M., Dallago, R., de Oliveira, D., Oliveira, J. V., & Treichel, H. (2013). Enzymatic synthesis of fructooligosaccharides by inulinases from Aspergillus niger and Kluyveromyces marxianus NRRL Y-7571 in aqueous–organic medium. Food Chemistry, 138(1), 148–153.
Oseguera, M. P., Guereca, L., & Lopez-Munguia, A. (1996). Properties of levansucrase from Bacillus circulans. Applied Microbiology and Biotechnology, 45(4), 465–471.
Tieking, M., Kaditzky, S., Valcheva, R., Korakli, M., Vogel, R. F., & Gänzle, M. G. (2005). Extracellular homopolysaccharides and oligosaccharides from intestinal lactobacilli. Journal of Applied Microbiology, 99(3), 692–702.
Baciu, I. E., Jördening, H. J., Seibel, J., & Buchholz, K. (2005). Investigations of the transfructosylation reaction by fructosyltransferase from B. subtilis NCIMB 11871 for the synthesis of the sucrose analogue galactosyl-fructoside. Journal of Biotechnology, 116(4), 347–357.
Li, W., Yu, S., Zhang, T., Jiang, B., & Mu, W. (2017). Synthesis of raffinose by transfructosylation using recombinant levansucrase from Clostridium arbusti SL206. Journal of the Science of Food and Agriculture, 97(1), 43–49.
Morales-Arrieta, S., Rodríguez, M. E., Segovia, L., López-Munguía, A., & Olvera-Carranza, C. (2006). Identification and functional characterization of levS, a gene encoding for a levansucrase from Leuconostoc mesenteroides NRRL B-512 F. Gene, 376(1), 59–67.
Sandkvist, M. (2001). Biology of type II secretion. Molecular Microbiology, 40(2), 271–283.
Kralj, S. (2004). Glucansucrases of lactobacilli. Journal of Biological Chemistry, 276, 44557–44562.
Nurizzo, D., Turkenburg, J. P., Charnock, S. J., Roberts, S. M., Dodson, E. J., McKie, V. A., Taylor, E. J., Gilbert, H. J., & Davies, G. J. (2002). Cellvibrio japonicus α-L-arabinanase 43A has a novel five-blade β-propeller fold. Nature Structural & Molecular Biology, 9(9), 665–668.
Meng, G., & Fütterer, K. (2003). Structural framework of fructosyl transfer in Bacillus subtilis levansucrase. Nature Structural & Molecular Biology, 10(11), 935–941.
Martínez-Fleites, C., Ortíz-Lombardía, M., Pons, T., Tarbouriech, N., Taylor, E. J., Arrieta, J. G., Hernández, L., & Davies, G. J. (2005). Crystal structure of levansucrase from the gram-negative bacterium Gluconacetobacter diazotrophicus. Biochemical Journal, 390(1), 19–27.
Yanase, H., Maeda, M., Hagiwara, E., Yagi, H., Taniguchi, K., & Okamoto, K. (2002). Identification of functionally important amino acid residues in Zymomonas mobilis levansucrase. Journal of Biochemistry, 132(4), 565–572.
Flores-Maltos, D. A., Mussatto, S. I., Contreras-Esquivel, J. C., Rodríguez-Herrera, R., Teixeira, J. A., & Aguilar, C. N. (2016). Biotechnological production and application of fructooligosaccharides. Critical Reviews in Biotechnology, 36(2), 259–267.
Guo, M., Chen, G., & Chen, K. (2016). Fructooligosaccharides: effects, mechanisms, and applications (pp. 51–63). Springer New York: In research progress in oligosaccharins.
Patel, S., & Goyal, A. (2012). The current trends and future perspectives of prebiotics research: a review. 3. Biotech, 2(2), 115–125.
Dominguez, L. J., Martínez-González, M. A., Basterra-Gortari, F. J., Gea, A., Barbagallo, M., & Bes-Rastrollo, M. (2014). Fast food consumption and gestational diabetes incidence in the SUN project. PloS One, 9(9), e106627.
Chen, G., Li, C., & Chen, K. (2016). Fructooligosaccharides: A review on their mechanisms of action and effects. Studies in natural products chemistry: Bioactive Natural Products, 48, 209–229.
Gibson, G. R., Beatty, E. R., Wang, X., & Cummings, J. H. (1995). Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology, 108(4), 975–982.
Celligoi, M. A. P. C., dos Santos, D. A., da Silva, P. B., & Baldo, C. (2015). Fermented foods, part I biochemistry and biotechnology. Taylor & Francis Group: CRC Press.
Xiao, J., Sakaguchi, E., & Bai, G. (2016). Short-term supplementation with dietary fructooligosaccharide and dietary mannitol elevated the absorption of calcium and magnesium in adult rats. Czech Journal of Animal Science, 61(6), 281–289.
Coxam, V. (2007). Current data with inulin-type fructans and calcium, targeting bone health in adults. The Journal of Nutrition, 137, 2527S–2533S.
Acknowledgements
The authors acknowledge the Department of Biotechnology (DBT), Government of India. JSJ and LKN acknowledges Science and Engineering Research Board (SERB) N-PDF fellowships, PDF/2016/445 and PDF/2015/662, respectively.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Singh, S.P., Jadaun, J.S., Narnoliya, L.K. et al. Prebiotic Oligosaccharides: Special Focus on Fructooligosaccharides, Its Biosynthesis and Bioactivity. Appl Biochem Biotechnol 183, 613–635 (2017). https://doi.org/10.1007/s12010-017-2605-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-017-2605-2