Biosynthesis of Antibiotics from Microbial Symbionts of Sponges and Corals

  • Loganathan Karthik
  • Zhiyong LiEmail author


Sponges and corals are significant sources for marine natural products. They have a pool of novel microorganisms. Due to low cost of gene sequencing, in recent years, several reports are available for novel compounds from sponge- and coral-associated microorganisms. Still, most of the biosynthesis mechanisms are not revealed. There are only few reports on the biosynthesis mechanism of antibiotics from sponge- and coral-associated microorganisms. The scanty amount of antibiotic was produced by most of the strains; hence it is important to explore the biosynthesis of antibiotics to improve the production. In this chapter, we cover the important reports of biosynthesis of antibiotics from microbial symbionts especially sponges and corals.


Sponges Corals Symbionts Biosynthesis Antibiotics 



We gratefully acknowledge the financial supports from the National Natural Science Foundation of China (NSFC) (31861143020, 41776138), High-Tech Research and Development Program of China (2013AA092901, 2011AA090702, 2007AA09Z447, 2004AA628060, 2002AA608080) and Chinese Post-Doctoral Funding (No: 15005188).


  1. 1.
    Newmann DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981–2002. J Nat Prod. 2013;66:1022–37.CrossRefGoogle Scholar
  2. 2.
  3. 3.
    Andersen RJ, Williams DE. Pharmaceuticals from the sea. In: Harrison RM, Hester RE, editors. Environmental science and technology. Cambridge: The Royal society of Chemistry; 2000.Google Scholar
  4. 4.
    Lindel T, Jensenm PR, Fenical W, Long BH, Casazza AM, Carboni J, et al. Eleutherobin, a new cytotoxin that mimics paclitaxel (Taxol) by stabilizing microtubules. J Am Chem Soc. 1997;119:8744–5.CrossRefGoogle Scholar
  5. 5.
    Ter Haar E, Kowalski RJ, Hamel E, Lin CM, Longley RE, Gunasekera SP, et al. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemist. 1996;35:243.CrossRefGoogle Scholar
  6. 6.
    Khosla C, Gokhale RS, Jacobsen JR, Cane DE. Tolerance and specificity of polyketide synthases. Annu Rev Biochem. 1999;68:219–53.CrossRefGoogle Scholar
  7. 7.
    Jenke-Kodama H, Sandmann A, Müller R, Dittmann E. Evolutionary implications of bacterial polyketide synthases. Mol Biol Evol. 2005;22:2027–39.CrossRefGoogle Scholar
  8. 8.
    Cox RJ. Biosynthesis. Annu Rep Prog Chem Sect B. 2002;96:231–58.CrossRefGoogle Scholar
  9. 9.
    Wang H, Fewer DP, Holm L, Rouhiainen L, Sivonen K. Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes. Proc Natl Acad Sci. 2014;111:9259–64.CrossRefGoogle Scholar
  10. 10.
    Bushley KE, Turgeon BG. Phylogenomics reveals subfamilies of fungal nonribosomal peptide synthetases and their evolutionary relationships. BMC Evol Biol. 2010;10:26.CrossRefGoogle Scholar
  11. 11.
    Drake EJ, Miller BR, Shi C, Tarrasch JT, Sundlov JA, Leigh Allen C, Skiniotis G, et al. Structures of two distinct conformations of holo-non-ribosomal peptide synthetases. Nature. 2016;529:235–8.CrossRefGoogle Scholar
  12. 12.
    Mootz HD, Schwarzer D, Marahiel MA. Ways of assembling complex natural products on modular nonribosomal peptide synthetases. Chem Bio Chem. 2002;3:490–504.CrossRefGoogle Scholar
  13. 13.
    Martínez-Núñez MA, Lópezy López VE. Nonribosomal peptides synthetases and their applications in industry. Sus Chemi Proc. 2016;4:13.CrossRefGoogle Scholar
  14. 14.
    Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, et al. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep. 2013;30:108–60.CrossRefGoogle Scholar
  15. 15.
    McIntosh JA, Donia MS, Schmidt EW. Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat Prod Rep. 2009;26:537–59.CrossRefGoogle Scholar
  16. 16.
    Yang X, van der Donk WA. Ribosomally synthesized and post-translationally modified peptide natural products: new insights into the role of leader and core peptides during biosynthesis. Chemistry. 2013;19:7662–77.CrossRefGoogle Scholar
  17. 17.
    Tietz JI, Schwalen CJ, Patel PS, Maxson T, Blair PM, Tai H-C, Zakai UI, et al. A new genome-mining tool redefines the lasso peptide biosynthetic landscape. Nat Chem Biol. 2017;13:70–478.CrossRefGoogle Scholar
  18. 18.
    Kennedy EP. Hitler’s gift and the era of biosynthesis. J Biol Chem. 2001;276:42619–31.CrossRefGoogle Scholar
  19. 19.
    Liscum L. Cholesterol biosynthesis. In: Vance JE, Vance DE, editors. Biochemistry of lipids, lipoproteins and membranes. Amsterdam: Elsevier; 2008. p. 399–421.CrossRefGoogle Scholar
  20. 20.
    Bentley R. Secondary metabolite biosynthesis: the first century. Crit Rev Biotechnol. 1999;19:1–40.CrossRefGoogle Scholar
  21. 21.
    Bretschneider T, Heim JB, Heine D, Winkler R, Busch B, Kusebauch B, et al. Vinylogous chain branching catalysed by a dedicated polyketide synthase module. Nature. 2013;502:124–8.CrossRefGoogle Scholar
  22. 22.
    Bode HB, Daniela Reimer D, Fuchs SW, Kirchner F, Dauth C, Kegler C, et al. Determination of the absolute configuration of peptide natural products by using stable isotope labeling and mass spectrometry. Chem Eur J. 2012;18:2342–8.CrossRefGoogle Scholar
  23. 23.
    Rinkel J, Dickschat JS. Recent highlights in biosynthesis research using stable isotopes. Beilstein J Org Chem. 2015;11:2493–508.CrossRefGoogle Scholar
  24. 24.
    Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, et al. The Pfam protein families database. Nucleic Acids Res. 2002;30:276–80.CrossRefGoogle Scholar
  25. 25.
    Schmidt EW, Donia MS. Complex enzymes in microbial natural product biosynthesis, part A: overview articles and peptides. Methods Enzymol. 2009;458:575–95.CrossRefGoogle Scholar
  26. 26.
    Kalaitzis JA, Lauro FM, Neilan BA. Mining cyanobacterial genomes for genes encoding complex biosynthetic pathways. Nat Prod Rep. 2009;26:1447–65.CrossRefGoogle Scholar
  27. 27.
    Gross H. Genomic mining–a concept for the discovery of new bioactive natural products. Curr Opin Drug Discov Devel. 2009;12:207–19.PubMedGoogle Scholar
  28. 28.
    Piel J. Metabolites from symbiotic bacteria. Nat Prod Rep. 2009;26:338–62.CrossRefGoogle Scholar
  29. 29.
    Piel J, Hertweck C, Shipley PR, Hunt DM, Newman MS, Moore BS. Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate ‘Streptomyces maritimus’: evidence for the derailment of an aromatic polyketide synthase. Chem Biol. 2000;7:943–55.CrossRefGoogle Scholar
  30. 30.
    Fusetani N, Matsunaga S. Bioactive sponge peptides. Chem Rev. 1993;93:1793–806.CrossRefGoogle Scholar
  31. 31.
    Lane AL, Moore BS. A sea of biosynthesis: marine natural products meet the molecular age. Nat Prod Rep. 2011;28:411–28.CrossRefGoogle Scholar
  32. 32.
    Zhang W, Lu L, Lai Q, Zhu B, Li Z, Ying Xu Y, et al. Family-wide structural characterization and genomic comparisons decode the diversity-oriented biosynthesis of thalassospiramides by marine proteobacteria. J Biol Chem. 2016;291:27228–38.CrossRefGoogle Scholar
  33. 33.
    Jordan PA, Moore BS. Biosynthetic pathway connects cryptic ribosomally synthesized posttranslationally modified peptide genes with Pyrroloquinoline alkaloids. Cell Chem Biol. 2016;23:1504–14.CrossRefGoogle Scholar
  34. 34.
    El Gamal A, Agarwal V, Rahman I, Moore BS. Enzymatic reductive dehalogenation controls the biosynthesis of marine bacterial pyrroles. J Am Chem Soc. 2016;138:13167–70.CrossRefGoogle Scholar
  35. 35.
    Tang X, Li J, Millán-Aguiñaga N, Zhang JJ, O’Neill EC, Ugalde JA, et al. Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining. ACS Chem Biol. 2015;10:2841–9.CrossRefGoogle Scholar
  36. 36.
    Agarwal V, El Gamal AA, Yamanaka K, Poth D, Kersten RD, Schorn M, et al. Biosynthesis of polybrominated aromatic organic compounds by marine bacteria. Nat Chem Biol. 2014;10:640–7.CrossRefGoogle Scholar
  37. 37.
    Lane AL, Nam S-J, Fukuda T, Yamanaka K, Kauffman CA, Jensen PR, et al. Structures and comparative characterization of biosynthetic gene clusters for cyanosporasides, enediyne-derived natural products from marine actinomycetes. J Am Chem Soc. 2013;135:4171–4.CrossRefGoogle Scholar
  38. 38.
    Ross AC, Xu Y, Lu L, Kersten RD, Shao Z, Al-Suwailem AM, et al. Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria. J Am Chem Soc. 2013;135:1155–62.CrossRefGoogle Scholar
  39. 39.
    Xu Y, Kersten RD, Nam S-J, Lu L, Al-Suwailem AM, Zheng H, et al. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J Am Chem Soc. 2012;134:8625–32.CrossRefGoogle Scholar
  40. 40.
    Wilson MC, Nam S-J, Gulder TAM, Kauffman CA, Jensen PR, William Fenical W, et al. Structure and biosynthesis of the marine streptomycete ansamycin ansalactam A and its distinctive branched chain polyketide extender unit. J Am Chem Soc. 2011;133:1971–7.CrossRefGoogle Scholar
  41. 41.
    Jørgensen H, Degnes KF, Dikiy A, Fjaervik E, Klinkenberg G, Zotchev SB. Insights into the evolution of macrolactam biosynthesis through cloning and comparative analysis of the biosynthetic gene cluster for a novel macrocyclic lactam, ML-449. Appl Environ Microbiol. 2010;76:283–93.CrossRefGoogle Scholar
  42. 42.
    Wilson MC, Gulder TA, Mahmud T, Moore BS. Shared biosynthesis of the saliniketals and rifamycins in Salinispora arenicola is controlled by the sare1259-encoded cytochrome P450. J Am Chem Soc. 2010;132:12757–65.CrossRefGoogle Scholar
  43. 43.
    Carlson JC, Fortman JL, Anzai Y, Li S, Burr DA, Sherman DH. Identification of the tirandamycin biosynthetic gene cluster from Streptomyces sp. 307-9. Chem Bio Chem. 2010;11:564–72.CrossRefGoogle Scholar
  44. 44.
    Engelhardt K, Degnes KF, Zotchev SB. Isolation and characterization of the gene cluster for biosynthesis of the thiopeptide antibiotic TP-1161. Appl Environ Microbiol. 2010;76:7093–101.CrossRefGoogle Scholar
  45. 45.
    Jørgensen H, et al. Biosynthesis of macrolactam BE-14106 involves two distinct PKS systems and amino acid processing enzymes for generation of the aminoacyl starter unit. Chem Biol. 2009;16:1109–21.CrossRefGoogle Scholar
  46. 46.
    Fisch KM, Gurgui C, Heycke N, van der Sar SA, Anderson SA, Webb VL, et al. Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting. Nat Chem Biol. 2009;5:494–501.CrossRefGoogle Scholar
  47. 47.
    Schultz AW, Oh D-C, Carney JR, Williamson RT, Udwary DW, Jensen PR, et al. Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic peptides of marine actinobacterial origin. J Am Chem Soc. 2008;130:4507–16.CrossRefGoogle Scholar
  48. 48.
    Winter JM, Moffitt MC, Zazopoulos E, McAlpine JB, Dorrestein PC, Moore BS. Molecular basis for chloronium-mediated meroterpene cyclization: cloning, sequencing, and heterologous expression of the napyradiomycin biosynthetic gene cluster. J Biol Chem. 2007;282:16362–8.CrossRefGoogle Scholar
  49. 49.
    Sudek S, Lopanik NB, Waggoner LE, Hildebrand M, Anderson C, Haibin Liu H, et al. Identification of the putative bryostatin polyketide synthase gene cluster from “Candidatus Endobugula sertula”, the uncultivated microbial symbiont of the marine bryozoan Bugula neritina. J Nat Prod. 2007;70:67–74.CrossRefGoogle Scholar
  50. 50.
    Ramaswamy AV, Sorrels CM, Gerwick WH. Cloning and biochemical characterization of the hectochlorin biosynthetic gene cluster from the marine cyanobacterium Lyngbya majuscula. J Nat Prod. 2007;70:1977–86.CrossRefGoogle Scholar
  51. 51.
    Udwary DW, Zeigler L, Asolkar RN, Singan V, Lapidus A, Fenical W, et al. Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc Natl Acad Sci U S A. 2007;104:10376–81.CrossRefGoogle Scholar
  52. 52.
    Schmidt EW, Nelson JT, Rasko DA, Sudek S, Eisen JA, Haygood MG, et al. Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc Natl Acad Sci U S A. 2005;102:7315–20.CrossRefGoogle Scholar
  53. 53.
    Chang Z. Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula. J Nat Prod. 2004;67:1356–67.CrossRefGoogle Scholar
  54. 54.
    Edwards DJ, Marquez BL, Nogle LM, McPhail K, Goeger DE, Ann Roberts M, et al. Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem Biol. 2004;11:817–33.CrossRefGoogle Scholar
  55. 55.
    Edwards DJ, Gerwick WH. Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. J Am Chem Soc. 2004;126:11432–3.CrossRefGoogle Scholar
  56. 56.
    Moffitt MC, Neilan BA. Characterization of the nodularin synthetase gene cluster and proposed theory of the evolution of cyanobacterial hepatotoxins. Appl Environ Microbiol. 2004;70:6353–62.CrossRefGoogle Scholar
  57. 57.
    Piel J, Hui D, Wen G, Butzke D, Platzer M, Fusetani N, Matsunaga S. Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Natl Acad Sci U S A. 2004;101:6222–7.CrossRefGoogle Scholar
  58. 58.
    Chang Z, Flatt P, Gerwick WH, Nguyen VA, Willis CL, Sherman DH. The barbamide biosynthetic gene cluster: a novel marine cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl starter unit. Gene. 2002;296:235–47.CrossRefGoogle Scholar
  59. 59.
    Allen EE, Bartlett DH. Structure and regulation of the omega-3 polyunsaturated fatty acid synthase genes from the deep-sea bacterium Photobacterium profundum strain SS9. Microbiol. 2002;148:1903–13.CrossRefGoogle Scholar
  60. 60.
    Li A, Piel J. A gene cluster from a marine Streptomyces encoding the biosynthesis of the aromatic spiroketal polyketide griseorhodin A. Chem Biol. 2002;9:1017–26.CrossRefGoogle Scholar
  61. 61.
    Morita N, Tanaka M, Okuyama H. Biosynthesis of fatty acids in the docosahexaenoic acid-producing bacterium Moritella marina strain MP-1. Biochem Soc Trans. 2000;28:943–5.CrossRefGoogle Scholar
  62. 62.
    Lewis K, Epstein S, D’Onofrio A, Ling LL. Uncultured microorganisms as a source of secondary metabolites. J Antibiot (Tokyo). 2010;63:468–76.CrossRefGoogle Scholar
  63. 63.
    Cichewicz RH, Valeriote FA, Crews P. Psymberin, a potent sponge-derived cytotoxin from Psammocinia distantly related to the pederin family. Org Lett. 2004;6:1951–4.CrossRefGoogle Scholar
  64. 64.
    Komatsu M, Uchiyama T, Omura S, Cane DE, Ikeda H. Genome-minimized streptomyces host for the heterologous expression of secondary metabolism. Proc Natl Acad Sci U S A. 2010;107:2646–51.CrossRefGoogle Scholar
  65. 65.
    Tan GY, Deng K, Liu X, Tao H, Chang Y, Chen J, Chen K, et al. Heterologous biosynthesis of spinosad: an omics-guided large polyketide synthase gene cluster reconstitution in Streptomyces. ACS Synth Biol. 2017;6:995–1005.CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Marine Biotechnology Laboratory, State Key Laboratory of Microbial Metabolism, School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China

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