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1 Introduction

The biotechnological production of lactic acid (2-hydroxypropionic acid) as an example of a platform chemical for the subsequent processing (e.g. into PLA) is carried out in technical reactors by using a suitable strain. LA can be produced by several microorganisms classified into bacteria, fungi, yeast, cyanobacteria and algae (Abdel-Rahman et al. 2013; Thongchul 2013). Besides the wide group of Lactobacillus (Antonio et al. 1996; Hofvendahl and Hahn-Hägerdahl 1997; Berry et al. 1999; Fu and Mathews 1999; Kwon et al. 2001), other bacteria like Bacillus (Payot et al. 1999; Danner et al. 2002; Patel et al. 2004), Enterococcus (Walczak et al. 2012), Lactococcus (Ramchandran et al. 2012), Pediococcus (Zhao et al. 2013b), Streptococcus (Tang et al. 2013) and filamentous fungi (Martak et al. 2003), especially Rhizopus oryzae (Yin et al. 1997; Bai et al. 2004), were also used as production strains. These microorganisms convert easily monosaccharides like glucose or fructose into cell mass and LA. LA formation and cell growth are closely coupled in LA fermentation (Zacharof and Lovitt 2013). An overview about the utilization of different renewable resources for LA fermentation, other microorganisms and yields depending on several process parameters was given by Hofvendahl and Hahn-Hägerdal (2000) and Castillo Martinez et al. (2013).

Whereas the fermentation of glucose can be carried out efficiently, the bioconversion of the pentose fraction out of lignocellulosic feedstocks and residues presents a challenge. A lot of attention has therefore been focused on genetically engineering strains that can efficiently utilize both glucose and pentose and convert them to useful compounds. The metabolic engineering objectives so far have focused on higher yields, productivities and expanding the substrate and product spectra (Aristidou and Penttilä 2000; Hua et al. 2006; Singh et al. 2006; Ilmen et al. 2007; Adler et al. 2012).

For the industrial production of l-(+)-LA, it is necessary to provide cheap carbon sources that can be easily metabolized by lactic acid bacteria (LAB) and to obtain the optimal conditions of fermentation with higher yields and production rates (John et al. 2007).

The different microbes have achieved one or more improvements over the others, such as a broader substrate range, improved yield and productivity, reduction of nutritional requirements or improved optical purity of LA (Abdel-Rahman et al. 2013). In view of the above-mentioned several complex substrates, also the use of mixed cultures in fermentation may provide useful combinations of metabolic pathways for the utilization of complex raw materials containing a mixture of carbohydrates (Cui et al. 2011; Trontel et al. 2011; Secchi et al. 2012). Several genetic-engineering approaches have been exploited in order to improve performance, LA yield and optical purity by various microbial producers (Nagamori et al. 2013; Wu et al. 2013; Zhao et al. 2013a). An extensive review by Okano et al. (2010) provides a broad collection of genetically engineered microorganisms for LA production including their characteristics and applicability for fermentation processes, respectively.

2 Lactic Acid-Forming Bacteria

Important LA-forming bacteria include the genera Lactobacillus and Bifidobacteria. Also the genera Bacillus, Lactococcus, Streptococcus, Pediococcus and Enterococcus are able to produce LA. There are also reports about the LA fermentation by some yeast and fungi.

2.1 The Genus Lactobacillus

Lactobacillus (L.) is a very heterogeneous genus, comprising species with a large diversity of phenotypic, biochemical and physiological features. More than 70 species are recognized, and all are able to convert carbohydrates into LA. The most important LA-forming bacteria belong to this genus. These include L. acidophilus, L. brevis, L. casei, L. delbrueckii, L. fermentum, L. helveticus, L. plantarum, L. paracasei and L. rhamnosus.

2.1.1 Short Characteristics of the Genus Lactobacillus

The genus can be divided into three subgroups based on their type of fermentation: obligate homofermentative, obligate heterofermentative and facultative heterofermentative. Important features of this genus are summarized in Table 1.

Table 1 Characteristics of the genus Lactobacillus
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2.1.2 Carbohydrate Fermentation of Lactobacilli

The metabolism of carbohydrate utilization depends both on the kind of the sugar (e.g. hexoses, pentoses) and from the type of fermentation by the LAB. General, the fermentation types differ in the utilization of hexoses and pentoses.

2.1.2.1 Fermentation of Hexoses
2.1.2.1.1 Obligate Homofermentative LAB

In principle the obligate homofermentative LAB converted hexoses to lactate by the Embden-Meyerhof-Parnas (EMP) glycolytic pathway (Fig. 1) (Wood 1961; Kandler 1983; von Wright and Axelsson 2012).

Fig. 1
figure 1

Fermentation of hexoses in obligate homofermentative LAB, EMP pathway

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Glucose is first broken down in glycolysis to pyruvate. Pyruvate is reduced by the enzyme lactate dehydrogenase to lactate, which is present under physiological conditions in dissociated lactate ions and protons. During the glycolysis of glucose or fructose per molecule, two molecules lactate and ATP are formed, so that the sum of the equation homofermentative LA fermentation is

$$ {\mathrm{C}}_6{\mathrm{H}}_{12}{\mathrm{O}}_6 + 2\ \mathrm{A}\mathrm{D}\mathrm{P}\ \to\ 2\ {\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + 2\ \mathrm{A}\mathrm{T}\mathrm{P} $$

Pentoses and gluconate were not fermented by this pathway because of lack of enzyme phosphoketolase. This type of fermentation includes some species of the genus Lactobacillus. The important LA producers in this genus are L. acidophilus and L. delbrueckii (Hofvendahl and Hahn-Hägerdal 2000; Kwon et al. 2001).

2.1.2.1.2 Obligate Heterofermentative LAB

The pathway of obligate heterofermentative LA fermentation is formed by LAB, which had a lack of enzyme aldolase. This enzyme is required for the glycolysis of fructose-1,6-bisphosphate into the two phosphotriose dihydroxyacetone and glyceraldehyde. This type of fermentation includes organisms of the genera Leuconostoc, Weissella and Oenococcus as well as some species of the genus Lactobacillus (Hammes et al. 1991; Hammes and Vogel 1995). Important obligate heterofermentative LA producers are L. brevis, L. fermentum and L. reuteri. These bacteria can degrade hexoses in the phosphogluconate pathway (Fig. 2) to lactate, ethanol and CO2 or furthermore to acetate.

Fig. 2
figure 2

Fermentation of hexoses in heterofermentative LAB, phosphogluconate pathway

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During the fermentation of glucose per molecule, one molecule lactate and ATP are formed, so that the sum of the equation of heterofermentative LA fermentation is

$$ {\mathrm{C}}_6{\mathrm{H}}_{12}{\mathrm{O}}_6 + \mathrm{A}\mathrm{D}\mathrm{P}\ \to\ {\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + {\mathrm{C}}_2{\mathrm{H}}_5\mathrm{O}\mathrm{H} + {\mathrm{C}\mathrm{O}}_2 + \mathrm{A}\mathrm{T}\mathrm{P} $$

Other hexoses (such as mannose or fructose) enter the pathway as either glucose-6-phosphate or fructose-6-phosphate. Fructose, however, is reduced not only to lactate and CO2 but also to mannitol and acetate:

$$ 3\ {\mathrm{C}}_6{\mathrm{H}}_{12}{\mathrm{O}}_6 + {\mathrm{H}}_2\mathrm{O} + 2\ \mathrm{A}\mathrm{D}\mathrm{P}\ \to\ {\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + 2\ {\mathrm{C}}_6{\mathrm{H}}_{14}{\mathrm{O}}_6 + {\mathrm{C}}_2{\mathrm{H}}_4{\mathrm{O}}_2 + {\mathrm{C}\mathrm{O}}_2 + 2\ \mathrm{A}\mathrm{T}\mathrm{P} $$

For the fermentation of galactose, there are two different pathways, depending on the form it enters in the cells (von Wright and Axelsson 2012). If galactose enters the cells as galactose-6-phosphate, it will ferment also to pyruvate however via the tagatose-6-phosphate pathway (Bisset and Anderson 1974) (Fig. 3a). As a free galactose, imported in the cells by a specific permease, it will ferment via glycolysis to pyruvate by the so-called Leloir pathway (Kandler 1983) (Fig. 3b).

Fig. 3
figure 3

Fermentation of galactose in LAB, Leloir pathway

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2.1.2.2 Fermentation of Pentoses

Many LAB are able to ferment pentoses. They can only ferment heterofermentatively by entering the phosphogluconate pathway as either ribulose-5 phosphate or xylulose-5 phosphate (Kandler 1983) (Fig. 4). Pentoses (such as arabinose, ribose, xylose) are converted into lactate and acetate; CO2 is not produced. The sum of the equation is

Fig. 4
figure 4

Fermentation of various pentoses in LAB

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$$ {\mathrm{C}}_5{\mathrm{H}}_{10}{\mathrm{O}}_5 + 2\ \mathrm{A}\mathrm{D}\mathrm{P}\ \to\ {\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + {\mathrm{C}}_2{\mathrm{H}}_4{\mathrm{O}}_2 + 2\ \mathrm{A}\mathrm{T}\mathrm{P} $$

However, there are reports of homofermentative fermentation of pentoses by engineered strains of L. plantarum (Okano et al. 2009a, b).

2.1.2.2.1 Facultative Heterofermentative LAB

LAB, which can ferment hexoses and pentoses, belong to the group of facultative heterofermentative LAB. Hexoses are fermented by the EMP glycolytic pathway to lactate. Under glucose limitation some species can produce also ethanol, acetic acid and formic acid (Hammes and Hertel 2009). Pentoses enter this pathway and are fermented to LA and acetic acid. The important LA producers belong to this fermentation type, e.g. L. casei, L. plantarum and L. paracasei.

2.1.2.3 Fermentation of Other Important Carbohydrates

For the production of LA, the most important carbohydrates are the disaccharides lactose, maltose and sucrose. In principle they are split enzymatically into their monosaccharide, and then they enter the various pathways.

Lactose can enter the cells in two ways, either by means of a specific permease or as lactose-6-phosphate (von Wright and Axelsson 2012). In the first case, lactose is split into glucose and galactose, which can enter the major fermentation pathway (e.g. Streptococcus thermophilus). In the second case, lactose-6-phosphate is cleaved to glucose and galactose-6-phosphate. While glucose is processed by the glycolytic pathway, the galactose-6-phosphate enters the tagatose-6-phosphate pathway (e.g. Lactococcus lactic). In some cases both systems can coexist (Wood and Holzapfel 1995; von Wright and Axelsson 2012).

The fermentation of maltose is known; in lactococci the permease system is active (Sjöberg and Hahn-Hägerdahl 1989), while in various strains of L. sanfranciscensis, maltose is converted to glucose-1-phosphate and glucose (von Wright and Axelsson 2012).

In general, sucrose enters the cells also by a specific permease system, and it is split into glucose and fructose. Also it was reported that lactococci can convert lactose into glucose-6-phosphate and fructose (von Wright and Axelsson 2012).

Starch is fermented only by very few homofermentative species such as L. amylophilus (Altaf et al. 2006; Vishnu et al. 2006), L. manihotivorans (Morlon-Guyot et al. 1998; Ohkouchi and Inoue 2006) and L. amylovorus (Zhang and Cheryan 1991; Hammes and Hertel 2009). However, of these species L. amylophilus and L. manihotivorans are important for the production of LA (Altaf et al. 2007; Yen and Kang 2010; Son and Kwon 2013).

It is reported that the strain Lactobacillus plantarum SW14 has a potential for LA production directly from cassava starch under laboratory conditions (Bomrungnok et al. 2012). Also Enterococcus faecium was already described for the direct fermentation of starch containing feedstocks (Shibata et al. 2007; Nolasco-Hipolito et al. 2012).

2.1.3 Enantiomers of LA

An asymmetric C-atom LA exists in two enantiomeric forms l (+) and d (−) and in a racemic form (dl). The stereoisomeric composition of the formed LA by the various species of lactobacilli is enzymatically determined. The configuration of the LA l (+) or d (−) depends on the stereospecificity of the lactate dehydrogenase in the cells. Racemate (dl) formed either when d-(−)- and l-(+)-dehydrogenases are present in the same cells or when an inducible lactate racemate reacts with a constitutive l-(+)-lactate dehydrogenase (Hammes and Hertel 2009).

However Setter and Stetter and Kandler (1973) reported that the d-(−)-lactate formers produce d-(−)-lactate exclusively, whereas all l-(+)-lactate formers always produce a few percent of the other isomer. This is caused by the presence of an NAD-dependent d-lactate dehydrogenase of very low activity.

2.1.4 Characteristics of the Most Important Lactic Acid Producers

For the selection of strains for the LA production, the fermentation type, the fermented carbohydrates and the temperature of growth are very important. These typical facts for the most used LA producers in the genus Lactobacillus are summarized separately in Tables 2, 3 and 4 after the formation of the various LA enantiomer.

Table 2 Characteristics of Lactobacillus species produced l-(+)-LA
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Table 3 Characteristics of Lactobacillus species produced d-(−)-LA
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Table 4 Characteristics of Lactobacillus species produced dl-LA
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2.2 The Genus Bifidobacterium

There are many references of the use of bifidobacteria for LA production. Many investigations have shown that bifidobacteria promote health preferably via their application in the food industry (Shene et al. 2005; Popa and Ustunol 2011). From that perspective the interest has been focused more on the fermentation performance in combination with typical carbohydrates containing foodstuff (Buruleanu et al. 2011; Watson et al. 2012) than an industrial LA production (Li et al. 2008). In the genus Bifidobacterium (B.), B. adolescentis, B. animalis, B. bifidum, B. breve, B. longum and B. thermophilum are important LA producers.

2.2.1 Short Characteristics of the Genus Bifidobacterium

Important features of this genus are summarized in Table 5.

Table 5 Characteristics of the genus Bifidobacterium
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2.2.2 Carbohydrate Fermentation

Bifidobacteria ferment various types of sugars. Lactose, galactose and sucrose are metabolized by a large number of species. The bacteria lack enzyme aldolase (fructose-1,6-bisphosphate-aldolase), like other heterofermentative LAB, but they metabolize sugars via their own complicated pathway so-called bifid shout (De Vries and Stouthamer 1967) (Fig. 5). Hexoses are degraded via phosphoric esters of the hexoses, erythrose, glyceraldehyde and pentoses. At two sites acetyl-phosphate is cleaved and 2-glyceraldehyde-3-phosphate is formed. This is metabolized by the Embden-Meyerhof-Parnas pathway to l-(+)-lactic and acetic acid in the ratio 2:3 (Sgorbati et al. 1995). Gas is not produced. This pathway has a 25 % higher yield of ATP (2.5 moles per mole of glucose) as the homofermentative LA fermentation (2 moles per mole of glucose). The sum of the fermentation of glucose is

Fig. 5
figure 5

Fermentation of glucose and fructose by bifidobacteria, bifid shout

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$$ 2\ {\mathrm{C}}_6{\mathrm{H}}_{12}{\mathrm{O}}_6\ \to\ 2{\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + 3{\mathrm{C}}_2{\mathrm{H}}_4{\mathrm{O}}_2 + 5\ \mathrm{A}\mathrm{T}\mathrm{P} $$

Galactose is fermented by the Leloir pathway (Fig. 3) because the enzymes for this are basically available in glucose-grown cells. On this pathway gas is formed (Scardovi 1986).

The fermented carbohydrates from the most important species of the genus Bifidobacterium are summarized in Table 6.

Table 6 Fermentation of carbohydrates by important species of the genus Bifidobacterium
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2.3 The Order Bacillales

LA production is traditionally associated with non-spore-forming bacteria. In addition to these organisms, a number of LA-producing spore-forming bacteria have been described. They are allocated to the genera Bacillus and Sporolactobacillus. The most important LA producer in the genus Bacillus is the species Bacillus (B.) coagulans and in the genus Sporolactobacillus (S.) the species S. inulinus and S. laevolacticus.

2.3.1 The Genus Sporolactobacillus

The species S. inulinus and S. laevolacticus belong to the genus Sporolactobacillus, the only genus of the family of Sporolactobacillaceae. Important features of this genus are summarized in Table 7.

Table 7 Characteristics of the genus Sporolactobacillus
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The species S. inulinus (Fukushima et al. 2004; Wang et al. 2011; Zheng et al. 2012) and S. laevolacticus (Mimitsuka et al. 2012; Li et al. 2013) are important d-(−)-LA producers particularly because of their ability to metabolize starch and inulin (Table 8).

Table 8 Fermented carbohydrates of important species of the genus Sporolactobacillus
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2.3.2 Bacillus coagulans

A lot of species of the genus Bacillus (B.) are known for producing LA such as B. lentimorbus, B. popilliae, B. smithii, B. stearothermophilus, B. licheniformis and B. subtilis (Thomas et al. 1979; Claus and Berkeley (1986) Fritze and Claus 1995; Abdel-Rahman et al. 2013). One of the most important species forming LA is B. coagulans (Ou et al. 2011; Wang et al. 2012; Tashiro et al. 2013; Ma et al. 2014). Important features of this species are summarized in Table 9.

Table 9 Characteristics of B. coagulans
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Glucose is mainly fermented to l-(+)-LA and smaller amounts of 2.3-butanediol, acetoin, acetic acid and ethanol (Fritze and Claus 1995). Some strains of B. coagulans are able to ferment hexoses and pentoses homolactic to l-(+)-LA (Wang et al. 2012; Ou et al. 2011).

2.4 Other LA-Forming Microorganisms

Besides the previously described species of the genera Lactobacillus, Bifidobacteria, Bacillus and Sporolactobacillus, there are a few bacteria of different systematic positions that are significant for forming LA. The most important bacteria are Enterococcus faecium, Lactococcus lactis, Pediococcus acidilactici and Streptococcus thermophilus. Yeasts and fungi are also of increasingly economic importance such as Saccharomyces cerevisiae and Rhizopus oryzae. Since over 10 years there are reports from LA-producing E. coli strains. Most of them are described as metabolically engineered strains for the production of LA (Chang et al. 1999; Dien et al. 2001; Baba et al. 2006; Kim et al. 2013).

2.4.1 Enterococcus faecium

Compared to other LA-producing microorganisms, E. faecium does not play a major role for the industrial application, but it was already described for the direct fermentation of starch containing feedstocks (Shibata et al. 2007; Nolasco-Hipolito et al. 2012). Important features of E. faecium are summarized in Table 10.

Table 10 Characteristics of E. faecium
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2.4.2 Lactococcus lactis

From the family of Streptococcaceae, the species Lactococcus lactis (L. lactis) and Streptococcus thermophilus are particularly very important for LA production. The species of the genus Lactococcus differ from the other LAB by their pH and by their salt and temperature tolerance for growth (Table 9). Among LAB, L. lactis is the most extensively studied regarding its physiology, metabolic pathways and regulatory mechanisms. Its genome was the first LAB genome to be completely sequenced (Oliveira et al. 2005). Important features of L. lactis are summarized in Table 11.

Table 11 Characteristics of L. lactis
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Among the subspecies of L. lactis, L. lactis ssp. lactis (John et al. 2007) and L. lactis ssp. cremoris are most important for the production of LA (Ramchandran et al. 2012; Mukisa et al. 2012). Fermented carbohydrates of the important species are arranged in Table 12.

Table 12 Fermented carbohydrates in L. lactis subspecies (Teuber 2009)
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It is reported in the literature that L. lactis produce LA as the sole metabolic product at high dilution rates during continuous cultivations or at high glucose concentrations during batch growth (Benthin 1994; Melchiorsen et al. 2002). In contrast, growth at low dilution rates in continuous conditions or at low concentrations of glucose in batch conditions results in a mixed-acid fermentation, where formate, ethanol and acetate are produced in a molar ratio of 2:1:1 (Melchiorsen et al. 2001).

2.4.3 Pediococcus acidilactici

There have been not much applications published for P. acidilactici (Hofvendahl and Hahn-Hägerdal (2000), Giurca and Levin (1992, 1993)), but the new strain DQ2 has been recently described, which is characterized by high-temperature tolerance, high lignocellulose-derived inhibitor resistance and high LA production performance in combination with simultaneous saccharification and fermentation at high-solids loading of corn stover (Dao et al. 2013; Zhao et al. 2013b). Important features of P. acidilactici are summarized in Table 13.

Table 13 Characteristics of P. acidilactici
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2.4.4 Streptococcus thermophilus

The classification and nomenclature of streptococci have undergone significant changes over the years. In recent years, based on biochemical characteristics as well as RNA analysis, members of the genus Streptococcus have been reclassified into Lactococcus, Vagococcus, Enterococcus and Streptococcus. This genus includes both significant human and animal pathogens but also nonpathogenic species, in particular S. thermophilus, for the production of food (especially milk, milk products and cheese) and LA, particularly on lactose-rich substrates (Hofvendahl and Hahn-Hägerdal 2000; Pescuma et al. 2008; Secchi et al. 2012; Tang et al. 2013). Important features of S. thermophilus are summarized in Table 14.

Table 14 Characteristics of S. thermophilus
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S. thermophilus, like other streptococci that ferment carbohydrates, produce l-(+)-LA as well as minor amounts of acetic and formic acids, ethanol and CO2 (Whiley and Hardie 2009).

2.4.5 Saccharomyces cerevisiae

Recently, there are reports about LA-forming yeasts such as S. cerevisiae (Dequin and Barre 1994; Praphailong and Fleet 1997; Bianchi et al. 2001; Lu et al. 2012) and other Saccharomyces species, Zygosaccharomyces, Candida, Pichia and Kluyveromyces that have been engineered to produce LA (Abdel-Rahman et al. 2013). Important features of S. cerevisiae are summarized in Table 15.

Table 15 Characteristics of S. cerevisiae
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2.4.5.1 Carbohydrate Utilization

Under aerobic conditions, S. cerevisiae respire glucose, producing H2O and CO2. Under anaerobic conditions, cells ferment sugars to ethanol and CO2. Galactose and fructose are shown to be two of the best fermenting carbohydrates. S. cerevisiae do not ferment pentoses such as arabinose, ribose and xylose and also disaccharides, e.g. lactose and cellobiose. Glucose oxidation under aerobic conditions provides more energy than fermentation. Therefore, the mass increases rate, and the cell division rate in oxidative decomposition of sugar is much higher than in fermentation. The ability of yeasts to use different sugars can differ depending on the oxygen conditions. So some strains cannot grow anaerobically on sucrose and trehalose. d-(−)-lactate formation is described by Stewart et al. (2013) (Fig. 6).

Fig. 6
figure 6

d-(−)-Lactate production by S. cerevisiae (mod. Stewart et al. 2013)

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Experiments with S. cerevisiae under aerobic conditions demonstrated that during glucose consumption d-(−)-lactate forms as a result of methylglyoxal metabolism. The data suggest that increased glucose uptake by cells grown in a glucose-rich environment results in an increased generation of methylglyoxal with subsequent metabolism to d (−) lactate.

2.4.6 Rhizopus oryzae

It is known that the mould in the genera Rhizopus, Mucor and Monilia form LA (Yadav et al. 2011). Currently, there are increasing reports on the production of LA by various species of Rhizopus, especially R. oryzae but also R. arrhizus (Bai et al. 2008; Taskin et al. 2012; Wu et al. 2011). R. oryzae produce a wide spectrum of metabolites, in the form of enzymes, esters, organic acids, volatile materials, polymers and bioalcohols. Biodiesel can also be produced. The fungus is a rich source of LA but also fumaric acid and to a better extent malic acid (Ghosh and Ray 2011). R. oryzae is a filamentous fungus belonging to the traditional Zygomycota (Hibbett et al. 2007). Its important features are summarized in Table 16.

Table 16 Characteristics of R. oryzae
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2.4.6.1 Formation of LA

In R. oryzae, all fermentable carbon sources are metabolized to pyruvate during glycolysis (Fig. 7).

Fig. 7
figure 7

Fermentation routes of glucose in R. oryzae (mod. Meussen et al. 2012)

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The pyruvate is subsequently channelled to a number of pathways, including the pathways responsible for the formation of ethanol, lactate and fumarate. The dissolved oxygen in the medium influences the flow of pyruvate. Under anaerobic conditions, the carbon flow is directed towards the formation of ethanol, while under aerobic conditions, with excess of carbon substrate, the flow is directed towards organic acid production (Skory et al. 1998; Meussen et al. 2012). With a mutagenizing strain, they could express almost a tenfold increase in LA production compared to the parental strain. Also the formation of l-(+)-LA is possible by strains of R. oryzae or genetically modified strains (Bai et al. 2004 ; Park et al. 2004). R. oryzae is widely studied as a commercially perspective producer of l-(+)-LA (Miura et al. 2003; Yin et al. 1997; Yamane and Tanaka 2013), because the fungus cells possess better resistance to high concentrations of accumulated LA (Hamamci and Ryu 1994; Schepers et al. 2003). Moreover the cells need lower nutrient requirements compared to the commonly used bacterial producers (Hujanen et al. 2001; Kwon et al. 2000). The use of R. oryzae in immobilized form is one of the most efficient approaches to improve the LA production process for long-term acid production (Tay and Yang 2002; Efremenko et al. 2006; Yamane and Tanaka 2013).

2.4.7 Escherichia coli

There are many challenges for the industrial production of LA, and satisfying all these requirements is very difficult through the traditional use of LAB. Therefore, improving LAB via gene modification and using other microorganisms (e.g. E. coli) and yeast for LA production via gene modification have become an essential and interesting research area (Grabar et al. 2006; Okano et al. 2010). Several research activities are directed towards the recombinant improvement of LA yield and the optical purity since E. coli produces a mixture of organic acids and other metabolites (Zhou et al. 2012; Mazumdar et al. 2013; Zhao et al. 2013a). Important features of E. coli are summarized in Table 17.

Table 17 Characteristics of E. coli
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2.4.7.1 Lactate Formation

E. coli can grow both under aerobic and anaerobic conditions. Like other species of the family Enterobacteriaceae, E. coli ferments glucose anaerobically via pyruvate to various acids and gas. Pyruvate can be formed either via glycolysis or via the EMP or the Entner-Doudoroff (ED) pathway (Fig. 8). However, the ED pathway is by E. coli of minor importance, because the enzymes of the ED pathway are only induced at the presence of gluconate, glucuronate, galacturonate or idonate (Eisenberg and Dobrogosz 1967). The resulting pyruvate is converted to d-(−)-lactate, acetate, succinate and formate via so-called mixed-acid fermentation. Part of the formic acid is split into equal amounts of CO2 and H2. The sum of the equation is (Schlegel 2007)

Fig. 8
figure 8

Anaerobe fermentation of glucose by E. coli

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$$ {\mathrm{C}}_6{\mathrm{H}}_{12}{\mathrm{O}}_6\ \to\ 0.84\ {\mathrm{C}}_3{\mathrm{H}}_6{\mathrm{O}}_3 + 0.44\ {\mathrm{C}}_2{\mathrm{H}}_4{\mathrm{O}}_2 + 0.42\ {\mathrm{C}}_2{\mathrm{H}}_5\mathrm{O} + 0.29\ {\mathrm{C}}_4{\mathrm{H}}_6{\mathrm{O}}_4 + 0.02\ {\mathrm{C}\mathrm{H}}_2{\mathrm{O}}_2 + 0.44{\mathrm{C}\mathrm{O}}_2 + 0.43\ {\mathrm{H}}_2 + \mathrm{A}\mathrm{T}\mathrm{P} $$

Approximately 80 % of the glucose is fermented by these pathways, and the other 20 % are metabolized by the oxidative pentose phosphate pathway (Fuhrer et al. 2005).

3 Organic Lactate-Forming Bacteria

Various organic lactates are formed by LAB, such as 1,4-piperazinium-(l,l)-dilactate (Kamm et al. 1997; Richter et al. 2001), imidazole-(l)-lactate (Kamm et al. 1999), hexamethylenediamine-(l,l)-dilactate (Gutmacher 2008) and lysine-(l)-lactate (Leiss et al. 2010). Piperazinium-(l,l)-dilactate, imidazole-(l)-lactate (Kamm et al. 1999) and hexamethylenediamine-(l,l)-dilactate are applied as intermediates for the production of polylactic acid (Kamm et al. 1999, 2000). These lactates are formed by means of strains of Lactobacillus paracasei ssp. paracasei. Important features of L. paracasei ssp. paracasei are summarized in Table 18.

Table 18 Characteristics of L. paracasei ssp. paracasei
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LA is produced through facultative heterofermentation, which means cells of the strain ferment hexoses and pentoses (see Sect. 2.1). Hexoses are fermented by the EMP glycolytic pathway to l-(+)-lactate. The same strains, which are formerly described as L. pseudoplantarum, produce dl-LA (Hammes and Hertel 2009). Pentoses enter this pathway and are fermented to LA and acetic acid.

4 Platform Chemical Lactic Acid

Currently there are criteria for a platform chemical, such as multiple product applicability, high-volume product and potential industrial scaleup (Bozell and Petersen 2010). LA is widely used in the food, cosmetic, pharmaceutical and chemical application, such as lactic acid derivatives as dyeing assistants, and has received increased attention for use as a monomer for the production of biodegradable PLA (Datta et al. 1995; Kamm et al. 1997, 2000; Nampoothiri et al. 2010; Castillo Martinez et al. 2013). LA is one of the most interesting intermediates for the synthesis of industrial relevant bio-based compounds based on carbohydrates, and it was foreseen as a platform chemical for the production of several downstream chemicals. Lactic acid undergoes ready esterification to give lactate esters, of interest as new bio-based ‘green’ solvents (Kamm et al. 2008). Lactate esters have many potential markets as non-toxic replacements for halogenated and toxic solvents. The use of esters, e.g. ethyl lactate and butyl lactate as solvents for cellulose lacquers or poly(vinyl) compounds, is important, and a great variety of esters have been recommended for use as plasticizers in polymers. Catalytic reduction of lactic acid leads to propylene glycol, which can be further dehydrated to give propylene oxide. Alternatively, lactic acid can be dehydrated to give acrylic acid and esters, but in practice this conversion proceeds in low yield (Walkup 1991).

The global lactic acid demand was estimated to be 714.2 kilo tons in 2013, which is expected to reach 1,960.1 kilo tons by 2020, growing at a compound annual growth rate of 15.5 % from 2014 to 2020 (SpecialChem 2014). Growth in demand for LA and its salts and esters in industrial applications will be driven mainly by LA-based biodegradable polymers and, to a lesser degree, lactate solvents (Abdel-Rahman et al. 2013; Taskila and Ojamo 2013).

5 Intermediate and Speciality Chemicals: Organic Lactates

Aminium lactates, such as piperazinium dilactate, imidazole lactate and hexamethylenediamine dilactate, are applied as intermediates for the production of polylactic acid (Kamm et al. 2000) and for the manufacture of high purity lactic acid (Kamm et al. 1999). Aminium lactates can be applied directly as constituents of pharmaceutical and cosmetic products as well. Piperazine lactate has anthelmintic activity (Chatterjee et al. 1997). Imidazole lactate is useful as a topical antilipolytic (Carreras Ginjaume 1985) and lysine lactate can be applied as component in skin lotions (Parab 1995). The antimicrobial activities of protic ionic liquids with lactate ion were investigated intensively (Pernak et al. 2004).

6 Biotechnological Production of LA

Biotechnological processes and bio-based products are an interesting alternative compared to classical ones of chemistry. The so-called white biotechnology points to an emerging field in biotechnology with immense potentials via utilization of biocatalysts for the manufacture of industrial products. The goal is to develop a fermentation process based on the substitution of expensive nutrient supplements by cheaper materials from renewable resources due to their main proportion of the whole process costs (Akerberg and Zacchi 2000; Okano et al. 2010). Depending on the further processing of the LA (e.g. for bioplastics), the separation of impurities after fermentation is a major process cost too (Fitzpatrick et al. 2003; Ryu et al. 2012). Therefore an optimization is necessary to find a balance between the substitution of expensive nutrients and the limitation of interfering or undesirable components of natural raw materials, respectively.

The worldwide research is advancing focused on the use of renewable raw materials as carbon substrates as well as nutrient additive resources. In this context, there is a strong interest to reduce costs for raw materials and to use renewable resources.

With respect to the above-mentioned cost aspect of bioprocess feedstock, the utilization of residues and waste materials (Pintado et al. 1999; Huang et al. 2005; Bischoff et al. 2010; Ouyang et al. 2013; Tang et al. 2013) and agricultural by-products (Thomsen 2005; John 2009; Alonso et al. 2011; Li et al. 2012) became the focus of public attention.

LA was produced worldwide at first from glucose or pure starch on fermentative ways (Richter and Berthold 1998). First efforts for developing bioconversion processes for the production of LA directly from agricultural starchy feedstock were published by Shamala and Sreekantiah (1987). During the last years, starchy hydrolysates obtained from agricultural resources like corn or barley (Linko and Javanainen 1996; Oh et al. 2005; Venus and Richter 2006), cassava (Xiaodong et al. 1997; Bomrungnok et al. 2012), wheat (Hetenyi et al. 2010), rye (Otlewska et al. 2012), potatoes (Zhang and Jin 2010; Bilanovic et al. 2011) and sago (Nolasco-Hipolito et al. 2002) were also tested on their suitability as substrates for LA fermentation.

Lignocellulosic biomass represents the most abundant global source of biomass, and for this reason it has been largely utilized in many applications (Taherzadeh and Karimi 2007). Lignocellulosic materials can be used to obtain sugar solutions that may be usefully exploited for the production of LA through the following steps: (a) pretreatment to break down the lignocellulosic structure, (b) enzymatic hydrolysis to depolymerize lignocellulose to fermentative sugars, (c) sugar fermentation to LA by LAB and (d) separation and purification of LA (Moldes et al. 2006, Abdel-Rahman et al. 2011). In recent years, one of the most used processes to obtain LA from lignocellulosic materials is the simultaneous saccharification and fermentation (John et al. 2009; Qi et al. 2011; Zhao et al. 2013b), which is able to prevent enzyme inhibition by the product (Gullon et al. 2007; Castillo Martinez et al. 2013).

LAB need, besides the carbon source, also a source of nitrogen and other nutrients and phosphorus. The latter is available when inorganic phosphate salts are added to the medium. The demand for nitrogen cannot be covered by inorganic salts only. LAB need also a series of nitrogen-containing nutrients (amino acids, peptides, etc.) for growth, and therefore, the medium has to be supplied by complex protein hydrolysates (yeast extract, peptone, etc.). The protein extracts mentioned are very expensive, and their substitution by low-priced nutrient extracts is necessary when a large-scale production is planned. A useful combination of green biomass processing for the production of fodder pellets and the utilization of the pressed juice for the LA fermentation was described by Andersen and Kiel (2000) and Vodnar et al. (2010). The use of date juice together with different nitrogen sources as a substrate for LA production was investigated by Nancib et al. (2001).

7 Future Perspectives

Although LA production by LAB is very efficient, further improvements in the process can help make it more cost competitive with petroleum-based polymers for PLA production. Environmentally friendly, ‘green’ solvents are another potential area for lactic acid derivatives, particularly lactate esters of low-molecular-weight alcohols such as ethyl, propyl and butyl lactate (John et al. 2007; Delgado et al. 2010). From that perspective the lactate esters have also further applications in order to run alternative downstream technology (Kamble et al. 2012) and PLA polymerization process (Marques et al. 2012).

Yield and purity of the LA produced are currently limited by many factors including the production of both l- and d-LA via l-lactate dehydrogenase and d-lactate dehydrogenase, respectively, low yield due to by-product formation, use of nutritionally rich medium, high risk of bacteriophage infection that results in cell lysis and subsequent cessation of LA production (Abdel-Rahman et al. 2013). In addition to the previously used LAB and LA-producing microorganisms, these organisms are interesting for the production of LA that were until now get low attention such as microalgae and cyanobacteria.

Through different approaches, these defects can be partially remedied today. The usage of mixed strains and/or development of phage-resistant strains can prevent bacteriophage infection (Hassan and Frank 2001).

Various studies have investigated methods to overcome some problems in the field of metabolic engineering of the strains, e.g. improvement of optical purity via the deletion of either d- or l-LDH genes (Kyla-Nikkila et al. 2000) and increased LA yields through the reduction of by-product levels by the deletion of genes encoding pyruvate formate lyase (formic acid production), alcohol dehydrogenase (ethanol production) and/or acetate kinase (acetic acid production) (Zhou et al. 2003a).

Moreover, the development of bacterial strains producing LA on chemically defined media (Zhou et al. 2003b) and strains improving blocking steps in the phage life cycle (Allison and Klaenhammer 1998; Forde and Fitzgerald 1999) is advanced.

Another way to more effective LA formation is the search for organisms that can tolerate high pH values. Alkaliphilic LAB strains may be promising producers of LA due to their tolerance to high pH levels that would minimize contamination problems during processing. Calabia et al. (2011) isolated an alkaliphilic Lactobacillus halophilus from a marine environment that produced 65.8 g/L of l-LA at pH 9.0. By comparison, the strategy of NatureWorks as the main global PLA producer is directed on the yeast fermentation at lower pH, thereby significantly reducing the use of calcium hydroxide and sulphuric acid, in turn resulting in significantly lower quantities of gypsum together with less energy demand for the entire process (Vink et al. 2010).

Also not yet used for the formation of LA are organisms such as microalgae and cyanobacteria. These photosynthetic microorganisms offer an alternative LA production approach and would allow carbohydrate feedstock costs to be eliminated. It has long been known that some microalgae have the ability to convert the starch they accumulated under light and aerobic conditions into organic matter, such as LA, ethanol, acetic acid and formic acid under dark and anaerobic conditions (Hirayama and Ueda 2004; Oost et al. 1989). There are also reports about the LA production by the microalgal species Nannochlorum sp. 26A4 from about 26 g/L d-LA production with an optical purity of 99.8 % from their starch (40 % content per dry weight) at yield of 70 % under dark and anaerobic conditions (Hirayama and Ueda 2004).

New strains with new properties alone will not lead to more efficient production of LA, but only in interaction with new raw materials, progress in fermentation technology as well as downstream processing development. Because of the relatively low price of LA, one of the major challenges in its large-scale fermentative production is the cost of the raw material. Lactic acid can be produced from a wide spectrum of carbon sources including starchy materials, many food industry by-products (e.g. molasses, whey), agro-industrial residues and by-products (e.g. lignocellulose hydrolysates, cottonseed hulls, corn cob, corn stalks, wheat bran, brewer’s spent grains) and various other renewable resources. Together with the need of low-cost carbon, there is an additional demand of suitable supplements, which should not cause additional costs and problems in view of impurities. Therefore, the kind of nutrients as well as the optimization of their concentration is essential. It is likely that one of the future trends in lactic acid production will end up in mixtures of different low-cost raw materials in order to avoid the use of expensive complex supplements (Taskila and Ojamo 2013; Koutinas et al. 2014).

Besides the strain optimization and alternative raw materials, the transition from traditional batch including repeated batch and fed-batch fermentation to continuous mode fermentation (Dey and Pal 2013; Gao and Ho 2013) with cell recycle (Venus 2009; Wee and Ryu 2009; Lee et al. 2014) as solutions with free cells and the use of immobilized cells in different reactor types (fixed or fluidized bed) could lead to further performance improvement. The number of downstream processing steps strongly influences the quality and the price of the product. Thus the total costs are determined mainly by the purification rather than by LA production using fermentation (Reimann 2006). Open sources provide only limited data about industrial product recovery processes, but the main technology steps are known for large-scale production of carboxylic acids and ongoing research activities are widely discussed (López-Garzón and Straathof 2014). If the disadvantages of traditional fermentation and recovery process are overcome combined with the huge amount of gypsum as a by-product, significant progress for lactic acid production can be expected in the near future.

Furthermore methods for combining the fermentation of lactic acid and production of chemical sequence products derived from lactic acid are required for the development of intermediates and speciality chemicals. A worthwhile approach could be the direct fermentation on organic lactates, such as substituted aminium lactates.