Abstract
Lack of sufficient pure natural compounds hinders further drug developments. The optimization of fermentation conditions is essential to enhance the yield of metabolites. Microbial genome analysis reveals the presence of a large number of cryptic biosynthetic gene clusters, and different strategies are there to trigger these gene pathways for the extensive study of natural product chemistry. Hence, the advanced technologies play a crucial role to achieve efficient discovery and productivity of novel microbial bioactive compounds. This chapter provides an outline on the mass production of microbial natural products derived from marine sponges and corals.
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17.1 Introduction
Natural products are unique bioactive compounds, which led to the initiation of drug discovery [1]. Marine invertebrates are unexploited and significant resources in the marine environment to discover novel bioactive compounds. Marine sponges and corals harbor diverse microbial communities, such as actinobacteria, fungi, archaea, and viruses [2, 3]; their bioactive natural products are substantial in the pharmaceutical industries as antimicrobial, anticancer, and immunosuppressants [4]. The developments of innovative technologies have overcomed the hurdles for the discovery and characterization of microbial bioactive natural products. The mass production of microbial bioactive compounds is a significant aspect of achieving effective yield for structural elucidation, bioactivity studies, and pharmaceutical applications.
17.2 Cultured Microbes Derived from Sponges and Corals
17.2.1 Sponges
Sponges inhabit a range of marine and freshwater systems [5], which form a close association with phylogenetically diverse microorganisms [2, 3]. Moreover, the sponges have acquired symbiotic microbial flora through parental sponges, surrounding water, or from other sources [6,7,8]. Microorganisms derived from the marine sponges are best sources for bioactive natural products [4, 9]. Extensive research of the past two decades on sponge symbiotic microbial communities revealed their phylogenetic diversity and biogeography [10,11,12] and their vital role in host metabolism and health [13,14,15].
The cultured actinomycetes derived from the marine sponges are Dietzia, Rhodococcus, Streptomyces, Salinispora, Marinophilus, Solwaraspora, Salinibacterium, Aeromicrobium marinum, Williamsia maris, and Verrucosispora [12, 16]. Morphological variants of actinobacteria were isolated from the marine sponge Haliclona sp., in the South China Sea, e.g., Streptomyces, Nocardiopsis, Micromonospora, and Verrucosispora [17]. Moreover, the marine sponge-associated actinomycetes, like Rhodococcus sp. RV157 (Dysidea avara) and Micromonospora sp. RV43 (Aplysina aerophoba), were isolated from Mediterranean sponges, and Actinokineospora sp. EG49 (Spheciospongia vagabunda) were isolated from the Red Sea sponge, as well as Nocardiopsis sp. SBT366 (Chondrilla nucula), Streptomyces sp. SBT343 (Petrosia ficiformis), Geodermatophilus sp. SBT350 (Chondrilla nucula), Streptomyces sp. SBT345 (Agelas oroides), Streptomyces sp. SBT346 (Petrosia ficiformis), and Micromonospora sp. SBT373 (Chondrilla nucula) [18]. Diversity analysis of cultural actinomycetes associated with 8 species of marine sponges reported the 13 genera, including 5 genera as the first records belong to the 10 families and order Actinomycetales from the South China Sea and the Yellow Sea [16]. 180 actinomycete strains including at least 14 new phylotypes within the genera Micromonospora, Verrucosispora, Streptomyces, Salinispora, Solwaraspora, Microbacterium, and Cellulosimicrobium were isolated from the Caribbean sponge and sediment samples [19]. The actinomycetes isolated from 15 species of sponges in the South China Sea consisted of 20 genera of 12 families, including the 3 rare genera, such as Marihabitans, Polymorphospora, and Streptomonospora [12]. The marine sponge Mycale sp. derived bacterial strains isolation reported from the genera Actinobacteria, Bacteroidetes, Gammaproteobacteria, Alphaproteobacteria, and Firmicutes [20]. Particularly, 14 new actinobacterial strains were isolated from 3 Mediterranean sponges [21].
Ascomycetous fungi, such as Sordariomycetes, Dothideomycetes, and Eurotiomycetes, are highly dominated in marine sponges [22]. Most of the marine sponges harbored some quite common fungal genera, such as Acremonium, Aspergillus, Fusarium, Penicillium, Phoma, and Trichoderma [23, 24], and few rare genera, such as Botryosphaeria, Epicoccum, Paraphaeosphaeria, and Tritirachium [25]. Besides, fungal strains belonging to Bartalinia and Volutella from Tethya aurantium and Schizophyllum, Sporidiobolus, Bjerkandera (Basidiomycota), and Yarrowia (Ascomycota) were isolated from marine sponges [24, 26]. Cultured fungal strains from 10 species of marine sponges in the South China Sea belonged to the predominant genera, viz., Aspergillus, Penicillium, and Volutella and the others, such as Ascomycete, Fusarium, Isaria, Plectosphaerella, Pseudonectria, Simplicillum, and Trichoderma [27].
17.2.2 Corals
Corals are sessile marine invertebrates belonging to the phylum Cnidaria, living in the compact colonies of many identical individual polyps. Corals are categorized into stony and soft corals. Stony corals are mainly reef-building scleractinian corals, and soft corals include a range of species, like gorgonians and sea pens in the subclass of Alcyonaria or Octocorallia [28]. Corals involve a mutually beneficial symbiosis with photosynthetic dinoflagellate algae Symbiodinium. The dynamic relationship between the corals and microorganisms plays a significant role in the coral health [29,30,31,32,33,34]. Microorganisms associated with corals influence the coral host physiology as well as coral reef ecosystem, like pathogen resistance and biogeochemical cycling of critical nutrients [28, 31]. Fewer reports are available on the isolation of coral-associated microorganisms through the culture-dependent methods [35], whereas the culture-independent studies have revealed the diverse microflora associated with corals [36,37,38,39,40,41,42,43,44].
Green sulfur bacteria, such as Alphaproteobacteria, Firmicutes and Planctomycetales (Montastraea annularis), and Gammaproteobacteria and Betaproteobacteria (M. cavernosa), have been detected in corals [34], and Alphaproteobacteria and Bacteroidetes were found in the soft coral Dendronephthya sp. [36]. Predominant bacterial strains belonging to Gamma-, Alpha-, and Betaproteobacteria, Bacteroidetes, Firmicutes, Actinomycetales, Planctomycetes, and Chlorobi were found to be associated with soft coral Alcyonium antarcticum [37]. Five new actinobacterial genera of Cellulomonas, Dermacoccus, Gordonia, Serinicoccus, and Candidatus Microthrix along with 19 common actinobacterial genera were reported from soft coral Alcyonium gracllimum and stony coral Tubastraea coccinea in the East China Sea [38].
Culture enrichment aided in the isolation of higher ascomycetes and basidiomycetes fungal taxa from the coral skeletons [39]. Cultured fungi belonging to genera of Aspergillus, Penicillium, Cladosporium, Fusarium, Microsphaeropsis, Paecilomyces, Phoma, Tilletiopsis, Gibberella, Isaria, Acremonium, Debaryomyces, Myrmecridium, and Nigrospora were isolated from six species of gorgonians from the South China Sea [45]. Fungi associated with coral Porites pukoensis have been isolated, with Aspergillus being predominant, and the others consisted of Penicillium, Cochliobolus, Acremonium, Rigidoporus, Gibberella, Eutypella, Didymellaceae, and Curvularia [46]. To date, fungal spatial and functional relationship with corals is still poorly understood, and very few researchers have broadly explored the fungi associated with soft corals to isolate novel biologically active compounds [47].
17.3 Natural Products from Microbes Derived from Sponges and Corals
The discovery of microbes associated with marine sponges and corals has led to their intense exploitation for an untapped resource of the novel bioactive compounds, for example, polyketides, terpenoids, alkaloids, and non-ribosomal peptides [48,49,50], which might be ample candidates for the invention of new drug leads for cancer, infectious diseases, and lipid metabolic disorders or as immunosuppressants. Marine Actinobacteria, e.g., Streptomyces, Micromonospora, Microthrix parvicella, and Acidimicrobium, and particularly obligate marine actinomycetes, Salinispora tropica and Salinispora arenicola, are the producers of bioactive microbial metabolites [51,52,53]. Marine sponge-derived fungi, especially endophytic, produce the most of marine natural products among the marine fungi [54]. Some metabolites isolated from microorganisms associated with sponges and corals are summarized in Table 17.1.
17.4 Mass Production of Natural Products from Cultured Microbes Derived from Sponges and Corals
The microorganisms are able to synthesize a vast number of primary and secondary metabolites. However the quantities produced are very low for the industrial scale in the view of the industrial biotechnologists [107]; hence, the mass production efficiency of the microbial bioactive metabolites needs to be improved.
17.4.1 Fermentation Optimization
The optimization of fermentation condition depends on the type of microbial strain and target metabolite [56,57,58, 62, 82,83,84,85, 92], since the standard conditions may not favor the expression of a majority of microbial biosynthetic pathways [70, 108, 109]. The fermentation optimization includes fermentation method and production medium (carbon and nitrogen sources), along with the physical-chemical factors which include salt concentration, pH, temperature, agitation, aeration, incubation time, and competition/interaction between microorganisms [110,111,112,113,114].The solid substrates are widely used for mass production of fungal metabolites, but not much preferred for actinomycetes and bacteria [92, 115,116,117].
The traditional method of one parameter each a time for factorial optimization might not produce accurate results, so the statistical methods are helpful in this aspect. The widely used statistical tools for the optimization of critical factors of mass production culture conditions are Plackett-Burman (PB) design and response surface methodology [62, 112, 113]. The PB design method is useful to select the critical control factors through the evaluation of the relative importance of bioprocess culture conditions and nutrients on the biomass and metabolite yield in liquid culture. The variables include the medium components, e.g., carbon and nitrogen sources, pH, temperature, incubation time, inoculum concentration, agitation, and aeration [111,112,113,114]. Response surface methodology (RSM) is useful to elucidate the interaction of selected critical variables of the bioprocess medium and selection of optimized conditions for the enhanced production of biomass and metabolite yield.
Different factors may hinder or induce the rate of biosynthesis of a novel or known marine microbial natural product or biomass during the mass production. The production medium, physicochemical factors, fermentation conditions, and carbon and nitrogen sources influence the efficient mass production and recovery of microbial natural products [70, 111,112,113, 117, 118]. The ideal conditions for growth and biosynthesis of secondary metabolites are not indeed the same, and even each organism obliges contrarily. The physiological and chemical regulators vary with diverse microorganisms and different metabolic pathways. Therefore, the individual optimal zones are required to improve the qualitative and quantitative secondary metabolite production. For instance, effective yield of antitrypanosomal active metabolite was observed from ISP2 medium with calcium alginate beads [70]. The sponge-associated fungus Aspergillus carneus was able to produce 3 new and 14 known compounds in the rice medium without sea salt than the rice medium with sea salt and modified Czapek medium [116]. Higher yield of (+)-terrein was achieved from the optimized mass production of Aspergillus terreus strain PF26 derived from a marine sponge than the un-optimized culture conditions [112]. Two new and one known lumazine peptides, along with a new cyclic pentapeptide, were isolated from the static, submerged fermentation of gorgonian-derived fungus Aspergillus sp. XS-20090B15. Further, L-methionine induced the isolation of new penilumamide B in comparison with traditional culture [93].
17.4.2 Efficient Finding and Preparation
Microorganisms are ubiquitous, and they thrive under different environmental conditions. Diverse habitats will influence different class of bioactive metabolites. Moreover, the production of microbial bioactive compounds will be affected by microbial strain selection, production mediums, fermentation conditions, microbial or chemical elicitors or inducers used, and the balance between biosynthesis and biotransformation during the mass production [70, 111,112,113,114,115,116,117,118,119].
A conventional method of natural product discovery depends on bioassay or chemotypes. Natural product discovery programs through traditional way are not supportive, time-consuming, laborious, and need more resources. Recent technologic advances have simplified the screening and efficient production of microbial bioactive natural products in addition to proposing the unique opportunity for re-establishment of microbial natural products as a more significant source of drug leads. The bacterial and fungal genome sequence information show the link between known natural products and the genes encoding their biosynthesis as analyzed by various software tools, such as antiSMASH, SMURF, CLUSEAN, ClustScan, and so on. Moreover, gene clusters and chemistry of the compounds progressively exploit to classify known natural products to discover new ones. Further, biosynthetic pathways responsible for the production of specific natural products enable a better understanding of mechanisms or interactions during the metabolite production under culture condition [120, 121].
The biosynthetic potential-based strain prioritization may help for natural product discovery, through pathway-specific probes [120] and high-throughput real-time PCR [121]. Moreover, the optimized mass production methods [94, 95, 112,113,114,115,116,117] and analytical approach of collective LC-MS and UV profile of each active extract help the systematic analysis, early de-replication, and screening with an LC-MS library to known or novel compounds [63,64,65,66, 122,123,124,125]. Comparative study has showed the utility of standard solvent partitioning (SSP) and accelerated solvent extraction methods (ASE) related to overall yields, solvent consumption, processing time, and chemical stability of both fractions [121]. In the past two decades, the excellent applications of combinatorial chemistry and high-throughput screening (HTS) technologies, genome sequencing, proteomics, metabolomics, and other methods have changed the entire scenario of finding natural products and the ways of harnessing its intricacies [126].
17.4.3 Activating Silent Gene Cluster
There are an increased number of cryptic or orphan pathways discovered; they are new sources to mine novel bioactive natural products. The developments in our understanding of microbial genome sequence, cluster arrangements, and metabolic pathways, and growth conditions, help to improve the natural product yield. Complete genome sequencing and mining are an alternate approach for the exploration of known or novel microbial species to analyze their metabolic potential [127]; however, these biosynthetic pathways are sometimes silent [128] or rarely expressed under standard laboratory conditions [129].
The traditional screening method incudes the selection of indigenous strain, followed by strain improvements through a series of mutational selection for the enhanced growth and metabolite yield [130]. It was suggested that new environments led to discover new microbial species to isolate novel bioactive natural products [131]. Thus, cryptic biosynthetic gene clusters could be activated by changing the cultural conditions. The OSMAC (one strain many compounds) principle is to mine and discover the new bioactive compounds through different approaches [132, 133].
17.4.3.1 Microbial Co-culture
Microorganisms show an active interspecies interaction with each other for available nutrients, space, and other resources for their existence in natural environments. Besides, the interaction may be beneficial or detrimental; the coexistence may incur production of novel bioactive secondary metabolites [134]. Therefore, microbial coexistence under laboratory conditions may induce activation of cryptic biosynthetic gene clusters which led to the innovative prospects. The co-culture strategy helps us to study the interspecies interactions responsible for the production of novel compounds with diverse structure and distinct bioactivities, such as antimicrobial and anticancer compounds [135]. Besides, this strategy has other benefits in comparison with pure cultures, such as in finding novel compounds or enhancing the yield of biological molecule, increase in the growth rate, and better utilization of mixed substrates. For example, based on the investigations of interspecies metabolic diversity of sponge-derived S. arenicola and S. pacifica, the S. pacifica induced the production of new rifamycins O and W from S. arenicola and known rifamycins and saliniketals [136]. Three new and ten known compounds isolated from sponge-derived Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 were the results of co-culture induced biosynthesis [67, 137]. A novel keyicin, a poly-nitroglycosylated anthracycline, was produced by the co-culture of marine ascidian-associated Micromonospora sp. Strain WMMB235 and marine sponge-associated Rhodococcus sp. Strain WMMA185. The biosynthetic gene cluster analysis of both strains and sequencing results of keyicin BGC confirm that the compound is from the Micromonospora sp. [126]. Though many researchers have conducted experiments on co-culture and synergistic microbial interactions, via coax between two or more than two microorganisms, but in reality, the challenges and questions related to the methods are still unanswered [138, 139].
17.4.3.2 Epigenetic Regulators
Putative biosynthetic gene regulators for the production of bioactive secondary metabolites of particular interest have been proved to be unique in different ways from previously understood models of gene regulation. The epigenetic regulators act as a signaling molecule by the regulation of putative biosynthetic genes and induce a variety of responses in microbes, for example, N-acetyl-D-glucosamine (GlcNAc), suberoylanilide hydroxamic acid (SAHA), DNA methyltransferase inhibitor (5-AZA), proteasome inhibitor (Bortezomib), and sodium citrate. The N-acetyl-D-glucosamine-mediated elicitation toward three sponge-derived actinomycetes led to the induced production of 3-formylindole and guaymasol in Micromonospora sp. RV43, the siderophore bacillibactin, and surfactin antibiotic in Rhodococcus sp. RV157 and improved the production of minor metabolites, actinosporins E–H in Actinokineospora sp. EG49 [140].
The influence of SAHA on Aspergillus terreus strain PF26 associated with a marine sponge in the biosynthesis of (+)-terrein was investigated. The epigenetic modifier shows the higher impact on (+)-terrein production than the control by stimulating the biosynthesis of the precursor, 6-hydroxymellein [141]. Optimized precursor-directed mutasynthesis has produced higher yield of BC194, a derivative of borrelidin from the Streptomyces rochei MB037 derived from the marine sponge Dysidea arenaria [78]. Bortezomib, a protease inhibitor, has induced the production of new bergamotene derivatives (xylariterpenoids H–K) from Pestalotiopsis maculans 16F-12 derived from marine sponge [91].
17.4.3.3 Gene Engineering
Majority of microbial natural product biosynthetic gene clusters (BGCs), relatively under standard laboratory conditions, are either transcriptional silent or expressed at deficient level, so these are the significant challenges for the discovery of novel natural products [142]. Analysis of microbial genes responsible for the biosynthesis of secondary metabolites usually depends on gene knockout and heterologous expression. Hence, the BGC identification and manipulation are accessible from the complete genome sequencing [128, 143]. For this purpose, some sponge- and coral-associated microorganisms are yet to be cultivated to study their true biosynthetic potential for microbial natural product discovery [130, 144].
The actinomycetes, especially the genus Streptomyces, harbor dozens of BGCs per genome [145]. Recently, advanced activation of cryptic or silent BGCs was carried out through the genetic approaches, such as either to unlock the suppression of BGC gene expression in the native hosts [146] or directly bypass the regulatory system by refactoring and reconstructing controlling elements in BGCs in the heterologous hosts [147,148,149]. Heterologous microbial hosts are an unusual choice, to bypass the task of removing introns and stitching genes by PCR to ensure the correct expression in the model hosts, such as E. coli, yeasts, and filamentous fungi [150]. Eukaryotic microorganisms have large and complex gene networks. The complexity and lack of understanding of the physiology of filamentous fungi, compared to bacteria, have delayed rapid development of these organisms as highly efficient hosts for homologous or heterologous gene expression [151].The fungal biosynthetic gene clusters mRNA processing will be complicated for heterologous gene expression.
17.5 Summary and Future Perspectives
The microorganisms associated with marine sponges and corals are the primary sources of marine bioactive natural products, which are least studied and under exploration for the discovery of novel drug leads. Marine microbial bioactive natural products, which are majorly from Streptomyces and filamentous fungi, include terpenoids, polyketides, alkaloids, non-ribosomal peptides, phenazines, indolocarbazoles, sterols, butenolides, and cytochalasins. Optimized mass production studies are helpful to achieve high yield of microbial bioactive compounds. Lack of sufficient yield of the pure natural compounds hinders the analysis, structural elucidation, biological activity assays, and further drug developments. So, to achieve a higher yield of the compounds, further developments are required for mass production studies as well as to reduce the labor and other requirements. These aspects are helpful for the upcoming researchers to take up further challenges to produce the novel bioactive marine microbial natural products with pharmaceutical development potentials, such as antimicrobials, antituberculosis, and anticancer compounds.
References
Montaser R, Luesch H. Marine natural products: a new wave of drugs? Future Med Chem. 2011;3:1475–89.
Thomas T, Moitinho-Silva L, Lurgi M, Björk JR, Easson C, Astudillo-García C, et al. Diversity, structure and convergent evolution of the global sponge microbiome. Nat Commun. 2016;7:11870.
Moitinho-Silva L, Nielsen S, Amir A, Gonzalez A, Ackermann GL, Cerrano C, et al. The sponge microbiome. GigaScience. 2017;6:1–7.
Blunt JW, Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2018;35:8–53.
Hooper JNA, van Soest RWM. Systema Porifera: a guide to the classification of sponges. New York: Kluwer Academic/Plenum Publishers; 2002.
Hentschel U, Hopke J, Horn M, Friedrich AB, Wagner M, Hacker J, et al. Molecular evidence for a uniform microbial community in sponges from different oceans. Appl Environ Microbiol. 2002;68:4431–40.
Lafi FF, Fuerst JA, Fieseler L, Engels C, Goh WWL, Hentschel U. Widespread distribution of poribacteria in demospongiae. Appl Environ Microbiol. 2009;75:5695–9.
Webster NS, Taylor MW. Marine sponges and their microbial symbionts: love and other relationships. Environ Microbiol. 2012;14:335–46.
Palomo S, González I, de la Cruz M, Martín J, Tormo JR, Anderson M, et al. Sponge-Derived Kocuria and Micrococcus spp. as Sources of the new Thiazolyl Peptide Antibiotic Kocurin. Mar Drugs. 2013;11:1071–86.
Taylor MW, Thacker RW, Hentschel U. Genetics. Evolutionary insights from sponges. Science. 2007;316:1854–5.
Schmitt S, Tsai P, Bell J, Fromont J, Ilan M, Lindquist N, et al. Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges. ISME J. 2012;6:564–76.
Sun W, Zhang F, He L, Karthik L, Li Z. Actinomycetes from the South China Sea sponges: isolation, diversity, and potential for aromatic polyketides discovery. Front Microbiol. 2015;6:1048.
Vacelet J. Electron microscope study of the association between bacteria and sponges of the genus Verongia (Dictyoceratida). J Microsc Biol Cell. 1975;23:271–88.
Vacelet J, Donadey C. Electron microscope study of the association between some sponges and bacteria. J Exp Mar Biol Ecol. 1977;30:301–14.
Friedrich AB, Fischer I, Proksch P, Hacker J, Hentschel U. Temporal variation of the microbial community associated with the Mediterranean sponge Aplysina aerophoba. FEMS Microbiol Ecol. 2001;38:105–13.
Xi L, Ruan J, Huang Y. Diversity and biosynthetic potential of Culturable Actinomycetes associated with marine sponges in the China seas. Int J Mol Sci. 2012;13:5917–32.
Jiang S, Sun W, Chen M, Dai S, Zhang L, Liu Y, et al. Diversity of culturable actinobacteria isolated from marine sponge Haliclona sp. Antonie Van Leeuwenhoek. 2007;92:405–16.
Abdelmohsen UR, Pimentel-Elardo SM, Hanora A, Radwan M, Abou-El-Ela SH, Ahmed S, et al. Isolation, phylogenetic analysis and anti-infective activity screening of marine sponge-associated actinomycetes. Mar Drugs. 2010;8:399–412.
Vicente J, Stewart A, Song B, Hill RT, Wright JL. Biodiversity of Actinomycetes associated with Caribbean sponges and their potential for natural product discovery. Mar Biotechnol. 2013;15:413–24.
Su P, Wang DX, Ding SX, Zhao J. Isolation and diversity of natural product biosynthetic genes of cultivable bacteria associated with marine sponge Mycale sp. from the coast of Fujian, China. Can J Microbiol. 2014;60:217–25.
Versluis D, McPherson K, van Passel MWJ, Smidt H, Sipkema D. Recovery of previously uncultured bacterial genera from three Mediterranean sponges. Mar Biotechnol. 2017;19:454–68.
Caballero-George C, Bolanos J, De Leon LF, Ochoa E, Darias J, D’Croz L, et al. Fungal diversity in marine sponges from highly diverse areas in the Isthmus of Panama. In: Lang MA, Sayer MDJ, editors. Proceedings of the 2013 AAUS/ESDP Joint International Scientific Diving Symposium Curacao; 2013. pp. 23–30.
Wang G, Li Q, Zhu P. Phylogenetic diversity of culturable fungi associated with the Hawaiian sponges Suberites zeteki and Gelliodes fibrosa. Antonie Leeuwenhoek. 2008;93:163–74.
Wiese J, Ohlendorf B, Blumel M, Schmaljohann R, Imhoff JF. Phylogenetic identification of fungi isolated from the marine sponge Tethya aurantium and identification of their secondary metabolites. Mar Drugs. 2011;9:561–85.
Holler U, Wright AD, Matthee GF, Konig GM, Draeger S, Aust HJ, et al. Fungi from marine sponges: diversity, biological activity and secondary metabolites. Mycol Res. 2000;104:1354–65.
Yu Z, Zhang B, Sun W, Zhang F, Li Z. Phylogenetically diverse endozoic fungi in the South China Sea sponges and their potential in synthesizing bioactive natural products suggested by PKS gene and cytotoxic activity analysis. Fungal Divers. 2013;58:127–41.
Zhou K, Zhang X, Zhang F, Li Z. Phylogenetically diverse cultivable fungal community and polyketide synthase (PKS), non-ribosomal peptide synthase (NRPS) genes associated with the South China Sea sponges. Microb Ecol. 2011;62:644–54.
Sun W, Anbuchezhian R, Li Z. Association of Coral-Microbes, and the ecological roles of microbial symbionts in corals. In: Goffredo S, Dubinsky Z, editors. Medusa and her sisters: the Cnidaria, past, present and future. Springer Press. pp. 347–357
Ainsworth TD, Wasmund K, Ukani L, Seneca F, Yellowlees D, Miller D, et al. Defining the tipping point: a complex cellular life/death balance in corals in response to stress. Sci Rep. 2011;1:160.
Thompson JR, Rivera HE, Closek CJ, Medina M. Microbes in the coral holobiont: partners through evolution, development, and ecological interactions. Front Cell Infect Microbiol. 2015;176:1–20.
McDevitt-Irwin JM, Baum JK, Garren M, Vega Thurber RL. Responses of coral-associated bacterial communities to local and global stressors. Front Mar Sci. 2017;4:262.
Rohwer F, Seguritan V, Azam F, Knowlton N. Diversity and distribution of coral-associated bacteria. Mar Ecol Prog Ser. 2002;243:1–10.
Bourne DG, Morrow KM, Webster NS. Insights into the coral microbiome: underpinning the health and resilience of reef ecosystems. Annu Rev Microbiol. 2016;70:317–40.
Frias-Lopez J, Zerkle AL, Bonheyo GT, Fouke BW. Partitioning of bacterial communities between seawater and healthy, black band diseased, and dead coral surfaces. Appl Environ Microbiol. 2002;68:2214–28.
Galkiewicz JP, Stellick SH, Gray MA, Kellogg CA. Cultured fungal associates from the deep-sea coral Lophelia pertusa. Deep-Sea Res I. 2012;67:12–20.
Harder T, Lau SCK, Dobretsov S, Fang TK, Qian PY. A distinctive epibiotic bacterial community on the soft coral Dendronephthya sp. and antibacterial activity of coral tissue extracts suggest a chemical mechanism against bacterial epibiosis. FEMS Microbiol Ecol. 2003;43:337–47.
Webster NS, Bourne D. Bacterial community structure associated with the Antarctic soft coral, Alcyonium antarcticum. FEMS Microbiol Ecol. 2007;59:81–94.
Yang S, Sun W, Tang C, Jin L, Zhang F, Li Z. Phylogenetic diversity of Actinobacteria associated with soft coral Alcyonium gracllimum and stony coral Tubastraea coccinea in the East China Sea. Microb Ecol. 2013;66:189–99.
Kendrick B, Risk MJ, Michaelides J, Bergman K. Amphibious microborers: bioeroding fungi isolated from live and dead corals. Bull Mar Sci. 1982;32:862–7.
Bourne DG, Munn CB. Diversity of bacteria associated with the coral Pocillopora damicornis from the Great Barrier Reef. Environ Microbiol. 2005;7:1162–74.
Yakimov MM, Cappello S, Crisafi E, Tursi A, Savini A, Corselli C, et al. Phylogenetic survey of metabolically active microbial communities associated with the deep-sea coral Lophelia pertusa from the Apulian plateau, Central Mediterranean Sea. Deep-Sea Res. 2006;53:62–75.
Wegley L, Edwards RA, Rodriguez-Brito B, Liu H, Rohwer F. Metagenomic analysis of the microbial community associated with the coral Porites astreoides. Environ Microbiol. 2007;9:2707–19.
Hong MJ, Yu YT, Chen CA, Chiang PW, Tang SL. Influence of species specificity and other factors on bacteria associated with the coral Stylophora pistillata in Taiwan. Appl Environ Microbiol. 2009;75:7797–806.
Amend AS, Barshis DJ, Oliver TA. Coral-associated marine fungi form novel lineages and heterogeneous assemblages. ISME J. 2012;6:1291–301.
Zhang XY, Bao J, Wang GH, He F, Xu XY, Qi SH. Diversity and antimicrobial activity of culturable fungi isolated from six species of the South China Sea gorgonians. Microb Ecol. 2012;64:617–27.
Li J, Zhong M, Lei X, Xiao S, Li Z. Diversity and antibacterial activities of culturable fungi associated with coral Porites pukoensis. World J Microbiol Biotechnol. 2014;30:2551–8.
Putria DA, Radjasab OK, Pringgeniesc D. Effectiveness of marine fungal symbiont isolated from soft coral Sinularia sp from Panjang Island as antifungal. Prog Environ Sci. 2015;23:351–7.
Gunatilaka AAL, Wijeratne EMK. Natural products from bacteria and fungi, in Phytochemistry and Pharmacognosy. UNESCO-Encyclopedia of Life Support Systems (EOLSS). http://www.eolss.net/eolss_sitemap.aspx
Karuppiah V, Sun W, Li Z. Natural products of Actinobacteria derived from marine organisms. In studies in natural products chemistry, ed. Atta-ur-Rahman. 2016;48:417–41.
Hoffmeister D, Keller NP. Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep. 2007;24:393–416.
Montalvo NF, Mohamed NM, Enticknap JJ, Hill RT. Novel actinobacteria from marine sponges. Antonie Van Leeuwenhoek. 2005;87:29–36.
Berdy J. Bioactive microbial metabolites. J Antibiot. 2005;58:1–26.
Mincer TJ, Jensen PR, Kauffman CA, Fenical W. Widespread and persistent populations of a major new marine actinomycete taxon in ocean sediments. Appl Environ Microbiol. 2002;68:5005–11.
Bugni TS, Ireland CM. Marine-derived fungi: a chemically and biologically diverse group of microorganisms. Nat Prod Rep. 2004;21:143–63.
Indraningrat AAG, Smidt H, Sipkema D. Bioprospecting sponge-associated microbes for antimicrobial compounds. Mar Drugs. 2016;14:87.
Cheng C, Othman EM, Stopper H, Edrada-Ebel R, Hentschel U, Abdelmohsen UR. Isolation of Petrocidin a, a new cytotoxic cyclic dipeptide from the marine sponge-derived bacterium Streptomyces sp. SBT348. Mar Drugs. 2017;15:383.
Igarashi Y, Asano D, Sawamura M, In Y, Ishida T, Imoto M. Ulbactins F and G, polycyclic thiazoline derivatives with tumor cell migration inhibitory activity from Brevibacillus sp. Org Lett. 2016;18:1658–61.
Reimer A, Blohm A, Quack T, Grevelding CG, Kozjak-Pavlovic V, Rudel T, et al. Inhibitory activities of the marine streptomycete-derived compound SF2446A2 against chlamydia trachomatis and Schistosoma mansoni. J Antibiot. 2015;68:674–9.
Santos OCS, Soares AR, Machado FLS, Romanos MTV, Muricy G, Giambiagi-deMarval M, et al. Investigation of biotechnological potential of sponge-associated bacteria collected in Brazilian coast. Lett Appl Microbiol. 2015;60:140–7.
Karuppiah V, Li Y, Sun W, Feng G, Li Z. Functional gene-based discovery of phenazines from the actinobacteria associated with marine sponges in the South China Sea. Appl Microbiol Biotechnol. 2015;99:5939–50.
Eltamany EE, Abdelmohsen UR, Ibrahim AK, Hassanean HA, Hentschel U, Ahmed SA. New antibacterial xanthone from the marine sponge-derived Micrococcus sp. EG45. Bioorg Med Chem Lett. 2014;24:4939–42.
Sathiyanarayanan G, Gandhimathi R, Sabarathnam B, Seghal Kiran G, Selvin J. Optimization and production of pyrrolidone antimicrobial agent from marine sponge-associated Streptomyces sp. MAPS15. Bioprocess Biosyst Eng. 2014;37:561–73.
Ibrahim D, Nazari TF, Kassim J, Lim S-H. Prodigiosin—an antibacterial red pigment produced by Serratia marcescens IBRL USM 84 associated with a marine sponge Xestospongia testudinaria. J Appl Pharm Sci. 2014;4:1–6.
Skariyachan S, Rao AG, Patil MR, Saikia B, Bharadwaj Kn V, Rao Gs J. Antimicrobial potential of metabolites extracted from bacterial symbionts associated with marine sponges in coastal area of gulf of Mannar biosphere, India. Lett Appl Microbiol. 2014;58:231–41.
Kunz AL, Labes A, Wiese J, Bruhn T, Bringmann G, Imhoff JF. Nature’s lab for derivatization: new and revised structures of a variety of Streptophenazines produced by a sponge-derived Streptomyces strain. Mar Drugs. 2014;12:1699–714.
Harrington C, Reen F, Mooij M, Stewart F, Chabot J-B, Guerra A, et al. Characterisation of non-autoinducing Tropodithietic acid (TDA) production from marine sponge Pseudovibrio species. Mar Drugs. 2014;12:5960–78.
Dashti Y, Grkovic T, Abdelmohsen UR, Hentschel U, Quinn RJ. Production of induced secondary metabolites by a co-culture of sponge-associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Mar Drugs. 2014;12:3046–59.
Waters AL, Peraud O, Kasanah N, Sims J, Kothalawala N, Anderson MA, et al. An analysis of the sponge Acanthostrongylophora igens’ microbiome yields an actinomycete that produces the natural product manzamine a. Front Mar Sci. 2014;1:54.
Viegelmann C, Margassery LM, Kennedy J, Zhang T, O’Brien C, O’Gara F, et al. Metabolomic profiling and genomic study of a marine sponge-associated Streptomyces sp. Mar Drugs. 2014;12:3323–51.
Abdelmohsen UR, Cheng C, Viegelmann C, Zhang T, Grkovic T, Ahmed S, Quinn RJ, Hentschel U, Edrada-Ebel R. Dereplication strategies for targeted isolation of new Antitrypanosomal Actinosporins a and B from a marine sponge associated-Actinokineospora sp. EG49. Mar Drugs. 2014;12:1220–44.
Phelan RW, Barret M, Cotter PD, O’Connor PM, Chen R, Morrissey JP, et al. Subtilomycin: a new Lantibiotic from Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans. Mar Drugs. 2013;11:1878–98.
Abdelmohsen UR, Szesny M, Othman EM, Schirmeister T, Grond S, Stopper H, et al. Antioxidant and anti-protease activities of Diazepinomicin from the sponge-associated Micromonospora strain RV115. Mar Drugs. 2012;10:2208–21.
Pimentel-Elardo SM, Buback V, Gulder TAM, Bugni TS, Reppart J, Bringmann G, et al. New Tetromycin derivatives with anti-Trypanosomal and protease inhibitory activities. Mar Drugs. 2011;9:1682–97.
Devi P, Wahidullah S, Rodrigues C, Souza LD. The sponge-associated bacterium Bacillus licheniformis SAB1: a source of antimicrobial compounds. Mar Drugs. 2010;8:1203–12.
Pimentel-Elardo SM, Kozytska S, Bugni TS, Ireland CM, Moll H, Hentschel U. Anti-parasitic compounds from Streptomyces sp. strains isolated from Mediterranean sponges. Mar Drugs. 2010;8:373–80.
El-Gendy MA, El-Bondkly AA. Production and genetic improvement of a novel antimycotic agent, Saadamycin, against dermatophytes and other clinical fungi from endophytic Streptomyces sp. Hedaya48. J Ind Microbiol Biotechnol. 2010;37:831–41.
Schneemann I, Kajahn I, Ohlendorf B, Zinecker H, Erhard A, Nagel K, et al. Mayamycin, a cytotoxic polyketide from a Streptomyces strain isolated from the marine sponge Halichondria panicea. J Nat Prod. 2010;73:1309–12.
Li Y, Zhang F, Banakar S, Li Z. Comprehensive optimization of precursor-directed production of BC194 by Streptomyces rochei MB037 derived from the marine sponge Dysidea arenaria. Appl Microbiol Biotechnol. 2018;102:7865–75.
Yamada T, Umebayashi Y, Kawashima M, Sugiura Y, Kikuchi T, Tanaka R. Determination of the chemical structures of Tandyukisins B–D, isolated from a marine sponge-derived fungus. Mar Drugs. 2015;13:3231–40.
Song FH, Ren B, Chen CX, Yu K, Liu XR, Zhang YH, et al. Three new sterigmatocystin analogues from marine-derived fungus Aspergillus versicolor MF359. Appl Microbiol Biotechnol. 2014;98:3753–8.
Wang JF, Lin XP, Qin C, Liao SR, Wan JT, Zhang TY, et al. Antimicrobial and antiviral sesquiterpenoids from sponge-associated fungus, Aspergillus sydowii zsds1-f6. J Antibiot. 2014;67:581–3.
Subramani R, Kumar R, Prasad P, Aalbersberg W. Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp. Asian Pac J Trop Biomed. 2013;3:291–6.
Scopel M, Abraham W-R, Henriques AT, Macedo AJ. Dipeptide cis-cyclo(Leucyl-Tyrosyl) produced by sponge associated Penicillium sp. F37 inhibits biofilm formation of the pathogenic Staphylococcus epidermidis. Bioorg Med Chem Lett. 2013;23:624–6.
Ma XH, Lo LT, Zhu TJ, Ba MY, Li GQ, Gu QQ, et al. Phenylspirodrimanes with anti-HIV activity from the sponge-derived fungus Stachybotrys chartarum MXH-X73. J Nat Prod. 2013;76:2298–306.
Li D, Xu Y, Shao C-L, Yang R-Y, Zheng C-J, Chen Y-Y, et al. Antibacterial Bisabolane-type Sesquiterpenoids from the sponge-derived fungus Aspergillus sp. Mar Drugs. 2012;10:234–41.
Peng JX, Jiao JY, Li J, Wang W, Gu QQ, Zhu TJ, et al. Pyronepolyene C-glucosides with NF-kappa B inhibitory and anti-influenza a viral (H1N1) activities from the sponge-associated fungus Epicoccum sp. JJY40. Bioorg Med Chem Lett. 2012;22:3188–90.
Cohen E, Koch L, Thu KM, Rahamim Y, Aluma Y, Ilan M, et al. Novel terpenoids of the fungus Aspergillus insuetus isolated from the Mediterranean sponge Psammocinia sp. collected along the coast of Israel. Bioorg Med Chem. 2011;19:6587–93.
Manilal A, Sabarathnam B, Kiran GS, Sujith S, Shakir C, Selvin J. Antagonistic potentials of marine sponge associated fungi Aspergillus clavatus MFD15. Asian J Med Sci. 2010;2:195–200.
Lee Y, Li H, Hong J, Cho H, Bae K, Kim M, et al. Bioactive metabolites from the sponge-derived fungus Aspergillus versicolor. Arch Pharm Res. 2010;33:231–5.
Pruksakorn P, Arai M, Kotoku N, Vilchèze C, Baughn AD, Moodley P, et al. Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria. Bioorg Med Chem Lett. 2010;20:3658–63.
Li Y, Zhang F, Banakar S, Li Z. Bortezomib-induced new bergamotene derivatives xylariterpenoids H–K from sponge-derived fungus Pestalotiopsis maculans 16F-12. RSC Adv. 2019;9:599–608.
Chen M, Shao CL, Meng H, She Z-G, Wang C-Y. Anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the gorgonian-derived fungus Aspergillus sp. XS-20090B15. J Nat Prod. 2014;77:2720–4.
Chen M, Shao CL, Fu XM, Kong C-J, She Z-G, Wang C-Y. Lumazine peptides penilumamides B-D and the cyclic pentapeptide asperpeptide-a from a gorgonian-derived Aspergillus sp. fungus. J Nat Prod. 2014;77:1601–6.
Liu Z, Xia G, Chen S, Liu Y, Li H, She Z. Eurothiocin A and B, sulfur- containing benzofurans from a soft coral-derived fungus Eurotium rubrum SH-823. Mar Drugs. 2014;12:3669–80.
Shao CL, Wang CY, Wei MY, Gu Y-C, She Z-G, Qian P-Y, et al. Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton from the gorgonian-derived fungus Aspergillus sp. Bioorg Med Chem Lett. 2013;21:690–3.
Li HJ, Chen T, Xie YL, Chen WD, Zhu XF, Lan WJ. Isolation and structural elucidation of chondrosterins F-H from the marine fungus Chondrostereum sp. Mar Drugs. 2013;11:551–8.
Chen M, Shao CL, Fu XM, Xu R-F, Zheng J-J, Zhao D-L, et al. Bioactive indole alkaloids and phenyl ether derivatives from a marine-derived Aspergillus sp. fungus. J Nat Prod. 2013;76:547–53.
Wei MY, Li D, Shao CL, Deng D-S, Wang C-Y. (±)-Pestalachloride D, an antibacterial racemate of chlorinated benzophenone derivative from a soft coral-derived fungus Pestalotiopsis sp. Mar Drugs. 2013;11:1050–60.
Zheng CJ, Shao CL, Wu LY, Chen M, Wang K-L, Zhao D-L, et al. Bioactive phenylalanine derivatives and cytochalasins from the soft coral-derived fungus, Aspergillus elegans. Mar Drugs. 2013;11:2054–68.
Zheng CJ, Shao CL, Guo ZY, Chen J-F, Deng D-S, Yang K-L, et al. Bioactive hydroanthraquinones and anthraquinone dimers from a soft coral-derived Alternaria sp. fungus. J Nat Prod. 2012;75:189–97.
Li HJ, Xie YL, Xie ZL, Chen Y, Lam C-K, Lan W-J. Chondrosterins A-E, triquinane- type sesquiterpenoids from soft coral-associated fungus Chondrostereum sp. Mar Drugs. 2012;10:627–38.
Sun W, Peng C, Zhao Y, Li Z. Functional gene-guided discovery of type II polyketides from culturable actinomycetes associated with soft coral Scleronephthya sp. PLoS One. 2012;7:e42847.
Zhuang Y, Teng X, Wang Y, Liu P, Li G, Zhu W. New quinazolinone alkaloids within rare amino acid residue from coral-associated fungus, Aspergillus versicolor LCJ-5-4. Org Lett. 2011;13:1130–3.
Shao CL, Wu HX, Wang CY, Liu Q-A, Xu Y, Wei M-Y, et al. Potent antifouling resorcylic acid lactones from the gorgonian-derived fungus Cochliobolus lunatus. J Nat Prod. 2011;74:629–33.
Trisuwan K, Rukachaisirikul V, Kaewpet M, Phongpaichit S, Hutadilok-Towatana N, Preedanon S, et al. Sesquiterpene and xanthone derivatives from the sea fan-derived fungus Aspergillus sydowii PSU-F154. J Nat Prod. 2011;74:1663–7.
Wei MY, Wang CY, Liu QA, Shao C-L, She Z-G, Lin Y-C. Five sesquiterpenoids from a marine-derived fungus Aspergillus sp. isolated from a gorgonian Dichotella gemmacea. Mar Drugs. 2010;8:941–9.
Amagata T, Minoura K, Numata A. Gymnastatins F–H, cytostatic metabolites from the sponge-derived fungus Gymnascella dankaliensis. J Nat Prod. 2006;69:1384–8.
Uzair B, Ahmed N, Ahmad VU, Kousar F. A new antibacterial compound produced by an indigenous marine bacteria—fermentation, isolation, and biological activity. Nat Prod Res. 2006;20:1326–31.
Finore I, Di Donato P, Mastascusa V, Nicolaus B, Poli A. Fermentation technologies for the optimization of marine microbial exopolysaccharide production. Mar Drugs. 2014;12:3005–24.
Brinkmann CM, Marker A, Ipek Kurtböke D. An overview on marine sponge-symbiotic bacteria as unexhausted sources for natural product discovery. Diversity. 2017;9:40.
Yang LH, Miao L, Lee OO, Li X, Xiong H, Pang KL, et al. Effect of culture conditions on antifouling compound production of a sponge-associated fungus. Appl Microbiol Biotechnol. 2007;74:1221–31.
Yin Y, Gao Q, Zhang F, Li Z. Medium optimization for the high yield production of single (+)-terrein by Aspergillus terreus strain PF26 derived from marine sponge Phakellia fusca. Process Biochem. 2012;47:887–91.
Bashir ZA, Ahmad A, Md-Nor S, Usup G. Factors affecting bioactivity of secondary metabolites produced by Streptomyces sp. PT1 using Plackett-Burman design. Adv Environ Biol. 2012;6:3043–51.
Nagai K, Kamigiri K, Arao N, Suzumura K, Kawano Y, Yamaoka M, et al. YM-266183 and YM-266184, novel thiopeptide antibiotics produced by Bacillus cereus isolated from a marine sponge—I. taxonomy, fermentation, isolation, physico-chemical properties and biological properties. J Antibiot. 2003;56:123–8.
Tian YQ, Lin XP, Wang Z, Zhou XF, Qin XC, Kaliyaperumal K, et al. Asteltoxins with antiviral activities from the marine sponge-derived fungus Aspergillus sp. SCSIO XWS02F40. Molecules. 2016;21:34.
Özkaya FC, Ebrahim W, El-Neketi M, Tanrikul TT, Kalscheuer R, Müller WEG, et al. Induction of new metabolites from sponge-associated fungus Aspergillus carneus by OSMAC approach. Fitoterapia. 2018;131:9–14.
Grkovic T, Abdelmohsen UR, Othman EM, Stopper H, Edrada-Ebel R, Hentschel U, Quinn RJ. Two new antioxidant actinosporin analogues from the calcium alginate beads culture of sponge-associated Actinokineospora sp. strain EG49. Bioorg Med Chem Lett. 2014;24:5089–92.
Gao Y, Yu L, Peng C, Li Z, Guo Y. Diketopiperazines from two strains of South China Sea sponge-associated microorganisms. Biochem Syst Ecol. 2010;38:931–4.
Yin Y, Xu B, Li Z, Zhang B. Enhanced production of (+)-terrein in fed-batch cultivation of Aspergillus terreus strain PF26 with sodium citrate. World J Microbiol Biotechnol. 2013;29:441–6.
Xie P, Ma M, Rateb ME, Shaaban KA, Yu Z, Huang S-X, et al. Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for Diterpenoid-producing Actinomycetes. J Nat Prod. 2014;77:377–87.
Johnson TA, Morgan MVC, Aratow NA, Estee SA, Sashidhara KV, Loveridge ST, et al. Assessing pressurized liquid extraction for the high-throughput extraction of marine-sponge-derived natural products. J Nat Prod. 2010;73:359–64.
Cremen PA, Zeng L. High-throughput analysis of natural product compound libraries by parallel LC–MS evaporative light scattering detection. Anal Chem. 2002;74:5492–500.
Tormo JR, Garcia JB, DeAntonio M, Feliz J, Mira A, Diez MT, et al. A method for the selection of production media for actinomycete strains based on their metabolite HPLC profiles. J Ind Microbiol Biotechnol. 2003;30:582–8.
Lang G, Mayhudin NA, Maya I, Mitova MI, Sun L, Sun L, et al. Evolving trends in the dereplication of natural product extracts: new methodology for rapid, small-scale investigation of natural product extracts. J Nat Prod. 2008;71:1595–9.
Genilloud O, Gonzalez I, Salazar O, Martın J, Tormo JR, Vicente F. Current approaches to exploit actinomycetes as a source of novel natural products. J Ind Microbiol Biotechnol. 2011;38:375–89.
Adnani N, Chevrette MG, Adibhatla SN, Zhang F, Yu Q, Braun DR, et al. Co-culture of marine invertebrate-associated bacteria and interdisciplinary technologies enable biosynthesis and discovery of a new antibiotic, Keyicin. ACS Chem Biol. 2017;12:3093–102.
Zerikly M, Challis GL. Strategies for the discovery of new natural products by genome mining. Chembiochem. 2009;10:625–33.
Scherlach K, Hertweck C. Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem. 2009;7:1753–60.
Hertweck C. Hidden biosynthetic treasures brought to light. Nat Chem Biol. 2009;5:450–2.
Parekh S. Strain improvement. In: Schaechter M, editor. The desk encyclopedia of microbiology. San Diego: Elsevier/Academic; 2004. p. 960–73.
Keller M, Zengler K. Tapping into microbial diversity. Nat Rev Microbiol. 2004;2:141–50.
Zahner H, Drautz H, Weber W. Novel approaches to metabolite screening. In: Bu’lock JD, Nisbet LJ, Winstanley DJ, editors. Bioactive microbial products: search and discovery. New York: Academic; 1982. p. 51–70.
Bode HB, Bethe B, Hofs R, Zeeck A. Big effects from small changes: possible ways to explore nature’s chemical diversity. Chembiochem. 2002;3:619–27.
Fredrickson AG. Behavior of mixed cultures of microorganisms. Annu Rev Microbiol. 1977;31:63–87.
Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol. 2015;13:509–23.
Bose U, Hewavitharana AK, Vidgen ME, Ng YK, Shaw PN, Fuerst JA, et al. Discovering the recondite secondary metabolome Spectrum of Salinispora species: a study of inter-species diversity. PLoS One. 2014;9:e91488.
Cueto M, Jensen PR, Kauffman C, Fenical W, Lobkovsky E, Clardy J. Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge. J Nat Prod. 2001;64:1444–6.
Hesseltine CW. Microbiology of oriental fermented foods. Annu Rev Microbiol. 1983;37:575–601.
Adnani N, Vazquez-Rivera E, Adibhatla SN, Ellis GA, Braun DR, Bugni TS. Investigation of interspecies interactions within marine Micromonosporaceae using an improved co-culture approach. Mar Drugs. 2015;13:6082–98.
Dashti Y, Grkovic T, Abdelmohsen UR, Hentschel U, Quinn RJ. Actinomycete metabolome induction/suppression with N-Acetylglucosamine. J Nat Prod. 2017;80:828–36.
Xiao L, Yin Y, Sun W, Zhang F, Li Z. Enhanced production of (+)-terrein by Aspergillus terreus strain PF26 with epigenetic modifier suberoylanilide hydroxamic acid. Process Biochem. 2013;48:1635–9.
Ren H, Wang B, Zhao H. Breaking the silence: new strategies for discovering novel natural products. Curr Opin Biotechnol. 2017;48:21–7.
Fox EM, Howlett BJ. Secondary metabolism: regulation and role in fungal biology. Curr Opin Microbiol. 2008;11:481–7.
Gross H. Genomic mining-a concept for the discovery of new bioactive natural products. Curr Opin Drug Discov Devel. 2009;12:207–19.
Liu G, Chater KF, Chandra G, Niu G, Tan H. Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev. 2013;77:112–43.
Li SR, Li YY, Lu CH, Zhang JL, Zhu J, Wang HX, et al. Activating a cryptic ansamycin biosynthetic gene cluster to produce three new naphthalenic octaketide ansamycins with n-pentyl and n-butyl side chains. Org Lett. 2015;17:3706–9.
Bachmann BO, Van Lanen SG, Baltz RH. Microbial genome mining for accelerated natural products discovery: is a renaissance in the making? J Ind Microbiol Biotechnol. 2014;41:175–84.
Li YX, Li ZR, Yamanaka K, Xu Y, Zhang WP, Vlamakis H, et al. Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis. Sci Rep. 2015;5:9383.
Ross AC, Gulland LES, Dorrestein PC, Moore BS. Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. ACS Synth Biol. 2015;4:414–20.
Lubertozzi D, Keasling JD. Developing Aspergillus as a host for heterologous expression. Biotechnol Adv. 2009;27:53–75.
Palmer JM, Keller NP. Secondary metabolism in fungi: does chromosomal location matter? Curr Opin Microbiol. 2010;13:431–6.
Acknowledgments
We gratefully acknowledge financial supports provided from the Natural Science Foundation of China (NSFC) (31861143020, 41776138, 41742002, U1301131, 41176127, 41076077), and High-Tech Research and Development Program of China (2013AA092901, 2011AA090702, 2007AA09Z447, 2004AA628060, 2002AA608080).
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Banakar, S.P., Karthik, L., Li, Z. (2019). Mass Production of Natural Products from Microbes Derived from Sponges and Corals. In: Li, Z. (eds) Symbiotic Microbiomes of Coral Reefs Sponges and Corals. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1612-1_17
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