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New voyages to explore the natural product galaxy

  • Natural Products - Original Paper
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Journal of Industrial Microbiology & Biotechnology

Abstract

Natural products are a large family of diverse and complex chemical molecules that have roles in both primary and secondary metabolism, and over 210,000 natural products have been described. Secondary metabolite natural products are of high commercial and societal value with therapeutic uses as antibiotics, antifungals, antitumor and antiparasitic products and in agriculture as products for crop protection and animal health. There is a resurgence of activity in exploring natural products for a wide range of applications, due to not only increasing antibiotic resistance, but the advent of next-generation genome sequencing and new technologies to interrogate and investigate natural product biosynthesis. Genome mining has revealed a previously undiscovered richness of biosynthetic potential in novel biosynthetic gene clusters for natural products. Complementing these computational processes are new experimental platforms that are being developed and deployed to access new natural products.

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References

  1. Baltz RH (2017) Gifted microbes for genome mining and natural product discovery. J Ind Microbiol Biotechnol 44:573–588. https://doi.org/10.1007/s10295-016-1815-x

    Article  CAS  PubMed  Google Scholar 

  2. Baltz RH (2018) Natural product drug discovery in the genomic era: realities, conjectures, misconceptions, and opportunities. J Ind Microbiol Biotechnol. https://doi.org/10.1007/s10295-018-2115-4

    Article  PubMed  Google Scholar 

  3. Bentley SD, Chater KF, Cerdeno-Tarraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417:141–147. https://doi.org/10.1038/417141a

    Article  PubMed  Google Scholar 

  4. Blin K, Medema MH, Kottmann R, Lee SY, Weber T (2017) The antiSMASH database, a comprehensive database of microbial secondary metabolite biosynthetic gene clusters. Nucleic Acids Res 45:D555–d559. https://doi.org/10.1093/nar/gkw960

    Article  CAS  PubMed  Google Scholar 

  5. Blin K, Wolf T, Chevrette MG, Lu X, Schwalen CJ, Kautsar SA, Suarez Duran HG, de Los Santos ELC, Kim HU, Nave M, Dickschat JS, Mitchell DA, Shelest E, Breitling R, Takano E, Lee SY, Weber T, Medema MH (2017) AntiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification. Nucleic Acids Res 45:W36–w41. https://doi.org/10.1093/nar/gkx319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cohen LJ, Esterhazy D, Kim SH, Lemetre C, Aguilar RR, Gordon EA, Pickard AJ, Cross JR, Emiliano AB, Han SM, Chu J, Vila-Farres X, Kaplitt J, Rogoz A, Calle PY, Hunter C, Bitok JK, Brady SF (2017) Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature 549:48–53. https://doi.org/10.1038/nature23874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Donia MS, Fischbach MA (2015) HUMAN MICROBIOTA. Small molecules from the human microbiota. Science 349:1254766. https://doi.org/10.1126/science.1254766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Epstein SC, Charkoudian LK, Medema MH (2018) A standardized workflow for submitting data to the Minimum Information about a Biosynthetic Gene cluster (MIBiG) repository: prospects for research-based educational experiences. Stand Genom Sci 13:16. https://doi.org/10.1186/s40793-018-0318-y

    Article  Google Scholar 

  9. Erbilgin O, Ruebel O, Louie KB, Trinh M, de Raad M, Wildish T, Udwary DW, Hoover CA, Deutsch S, Northen TR, Bowen BP (2017) MAGI: a Bayesian-like method for metabolite, annotation, and gene integration. bioRxiv. https://doi.org/10.1101/204362

    Article  Google Scholar 

  10. Gomez-Escribano JP, Alt S, Bibb MJ (2016) Next generation sequencing of actinobacteria for the discovery of novel natural products. Mar Drugs 14:78. https://doi.org/10.3390/md14040078

    Article  CAS  PubMed Central  Google Scholar 

  11. Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM, Funabashi M, Taketani M, Donia MS, Nayfach S, Pollard KS, Craik CS, Cravatt BF, Clardy J, Voigt CA, Fischbach MA (2017) Discovery of reactive microbiota-derived metabolites that inhibit host proteases. Cell 168(517–526):e518. https://doi.org/10.1016/j.cell.2016.12.021

    Article  CAS  Google Scholar 

  12. Hadjithomas M, Chen IA, Chu K, Huang J, Ratner A, Palaniappan K, Andersen E, Markowitz V, Kyrpides NC, Ivanova NN (2017) IMG–ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes. Nucleic Acids Res 45:D560–d565. https://doi.org/10.1093/nar/gkw1103

    Article  CAS  PubMed  Google Scholar 

  13. Hadjithomas M, Chen IM, Chu K, Ratner A, Palaniappan K, Szeto E, Huang J, Reddy TB, Cimermancic P, Fischbach MA, Ivanova NN, Markowitz VM, Kyrpides NC, Pati A (2015) IMG–ABC: a knowledge base To fuel discovery of biosynthetic gene clusters and novel secondary metabolites. MBio 6:e00932. https://doi.org/10.1128/mBio.00932-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hoshino S, Onaka H, Abe I (2018) Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria. J Ind Microbiol Biotechnol. https://doi.org/10.1007/s10295-018-2100-y

    Article  PubMed  Google Scholar 

  15. Hoshino S, Wakimoto T, Onaka H, Abe I (2015) Chojalactones A–C, cytotoxic butanolides isolated from Streptomyces sp. cultivated with mycolic acid containing bacterium. Org Lett 17:1501–1504. https://doi.org/10.1021/acs.orglett.5b00385

    Article  CAS  PubMed  Google Scholar 

  16. Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y, Hattori M, Omura S (2003) Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat Biotechnol 21:526–531. https://doi.org/10.1038/nbt820

    Article  PubMed  Google Scholar 

  17. Katz L, Baltz RH (2016) Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43:155–176. https://doi.org/10.1007/s10295-015-1723-5

    Article  CAS  PubMed  Google Scholar 

  18. Keller NP (2015) Translating biosynthetic gene clusters into fungal armor and weaponry. Nat Chem Biol 11:671–677. https://doi.org/10.1038/nchembio.1897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kim E, Moore BS, Yoon YJ (2015) Reinvigorating natural product combinatorial biosynthesis with synthetic biology. Nat Chem Biol 11:649–659. https://doi.org/10.1038/nchembio.1893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kjærbølling I, Vesth TC, Frisvad JC, Nybo JL, Theobald S, Kuo A, Bowyer P, Matsuda Y, Mondo S, Lyhne EK, Kogle ME, Clum A, Lipzen A, Salamov A, Ngan CY, Daum C, Chiniquy J, Barry K, LaButti K, Haridas S, Simmons BA, Magnuson JK, Mortensen UH, Larsen TO, Grigoriev IV, Baker SE, Andersen MR (2018) Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species. Proc Nat Acad Sci USA. https://doi.org/10.1073/pnas.1715954115

    Article  PubMed  Google Scholar 

  21. Koh EI, Robinson AE, Bandara N, Rogers BE, Henderson JP (2017) Copper import in Escherichia coli by the yersiniabactin metallophore system. Nat Chem Biol 13:1016–1021. https://doi.org/10.1038/nchembio.2441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li J, Wang H, Kwon YC, Jewett MC (2017) Establishing a high yielding streptomyces-based cell-free protein synthesis system. Biotechnol Bioeng 114:1343–1353. https://doi.org/10.1002/bit.26253

    Article  CAS  PubMed  Google Scholar 

  23. Li S, Li Y, Lu C, Zhang J, Zhu J, Wang H, Shen Y (2015) Activating a cryptic ansamycin biosynthetic gene cluster to produce three new naphthalenic octaketide ansamycins with n-pentyl and n-butyl side chains. Org Lett 17:3706–3709. https://doi.org/10.1021/acs.orglett.5b01686

    Article  CAS  PubMed  Google Scholar 

  24. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455. https://doi.org/10.1038/nature14098. https://www.nature.com/articles/nature14098#supplementary-information

  25. Mendes R, Kruijt M, de Bruijn I, Dekkers E, van der Voort M, Schneider JH, Piceno YM, DeSantis TZ, Andersen GL, Bakker PA, Raaijmakers JM (2011) Deciphering the rhizosphere microbiome for disease-suppressive bacteria. Science 332:1097–1100. https://doi.org/10.1126/science.1203980

    Article  CAS  PubMed  Google Scholar 

  26. Moore SJ, Lai HE, Needham H, Polizzi KM, Freemont PS (2017) Streptomyces venezuelae TX-TL—a next generation cell-free synthetic biology tool. Biotech J. https://doi.org/10.1002/biot.201600678

    Article  Google Scholar 

  27. Mukherjee S, Seshadri R, Varghese NJ, Eloe-Fadrosh EA, Meier-Kolthoff JP, Goker M, Coates RC, Hadjithomas M, Pavlopoulos GA, Paez-Espino D, Yoshikuni Y, Visel A, Whitman WB, Garrity GM, Eisen JA, Hugenholtz P, Pati A, Ivanova NN, Woyke T, Klenk HP, Kyrpides NC (2017) 1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life. Nat Biotechnol 35:676–683. https://doi.org/10.1038/nbt.3886

    Article  CAS  PubMed  Google Scholar 

  28. Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T, Kikuchi H, Shiba T, Sakaki Y, Hattori M (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci USA 98:12215–12220. https://doi.org/10.1073/pnas.211433198

    Article  CAS  PubMed  Google Scholar 

  29. Onaka H, Mori Y, Igarashi Y, Furumai T (2011) Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Appl Environ Microbiol 77:400–406. https://doi.org/10.1128/aem.01337-10

    Article  CAS  PubMed  Google Scholar 

  30. Papenfort K, Silpe JE, Schramma KR, Cong JP, Seyedsayamdost MR, Bassler BL (2017) A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation. Nat Chem Biol 13:551–557. https://doi.org/10.1038/nchembio.2336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Patridge E, Gareiss P, Kinch MS, Hoyer D (2016) An analysis of FDA-approved drugs: natural products and their derivatives. Drug Disc Today 21:204–207. https://doi.org/10.1016/j.drudis.2015.01.009

    Article  CAS  Google Scholar 

  32. Pishchany G, Mevers E, Ndousse-Fetter S, Horvath DJ Jr, Paludo CR, Silva-Junior EA, Koren S, Skaar EP, Clardy J, Kolter R (2018) Amycomicin is a potent and specific antibiotic discovered with a targeted interaction screen. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1807613115

    Article  PubMed  Google Scholar 

  33. Reddy BV, Milshteyn A, Charlop-Powers Z, Brady SF (2014) eSNaPD: a versatile, web-based bioinformatics platform for surveying and mining natural product biosynthetic diversity from metagenomes. Chem Biol 21:1023–1033. https://doi.org/10.1016/j.chembiol.2014.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ren H, Wang B, Zhao H (2017) Breaking the silence: new strategies for discovering novel natural products. Curr Opin Biotechnol 48:21–27. https://doi.org/10.1016/j.copbio.2017.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rodrigues T, Reker D, Schneider P, Schneider G (2016) Counting on natural products for drug design. Nat Chem 8:531–541. https://doi.org/10.1038/nchem.2479

    Article  CAS  PubMed  Google Scholar 

  36. Shen B (2015) A new golden age of natural products drug discovery. Cell 163:1297–1300. https://doi.org/10.1016/j.cell.2015.11.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Skinnider MA, Dejong CA, Rees PN, Johnston CW, Li H, Webster AL, Wyatt MA, Magarvey NA (2015) Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM). Nucleic Acids Res 43:9645–9662. https://doi.org/10.1093/nar/gkv1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Skinnider MA, Merwin NJ, Johnston CW, Magarvey NA (2017) PRISM 3: expanded prediction of natural product chemical structures from microbial genomes. Nucleic Acids Res 45:W49–w54. https://doi.org/10.1093/nar/gkx320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Smanski MJ, Zhou H, Claesen J, Shen B, Fischbach MA, Voigt CA (2016) Synthetic biology to access and expand nature’s chemical diversity. Nat Rev Microbiol 14:135–149. https://doi.org/10.1038/nrmicro.2015.24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tietz JI, Schwalen CJ, Patel PS, Maxson T, Blair PM, Tai HC, Zakai UI, Mitchell DA (2017) A new genome-mining tool redefines the lasso peptide biosynthetic landscape. Nat Chem Biol 13:470–478. https://doi.org/10.1038/nchembio.2319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vorholt JA (2012) Microbial life in the phyllosphere. Nat Rev Microbiol 10:828–840. https://doi.org/10.1038/nrmicro2910

    Article  CAS  PubMed  Google Scholar 

  42. Xu F, Nazari B, Moon K, Bushin LB, Seyedsayamdost MR (2017) Discovery of a cryptic antifungal compound from Streptomyces albus J1074 using high-throughput elicitor screens. J Am Chem Soc 139:9203–9212. https://doi.org/10.1021/jacs.7b02716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang MM, Wong FT, Wang Y, Luo S, Lim YH, Heng E, Yeo WL, Cobb RE, Enghiad B, Ang EL, Zhao H (2017) CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol. https://doi.org/10.1038/nchembio.2341

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zhou Z, Xu Q, Bu Q, Guo Y, Liu S, Liu Y, Du Y, Li Y (2015) Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis. ChemBioChem 16:496–502. https://doi.org/10.1002/cbic.201402577

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work conducted by the U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, is supported under Contract no. DE-AC02-05CH11231. We thank Richard Baltz, Leonard Katz, David Hopwood and Arnold Demain for inspiration and guidance.

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  1. United States Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA

    Nigel J. Mouncey, Hiroshi Otani, Daniel Udwary & Yasuo Yoshikuni

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  1. Nigel J. Mouncey
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  2. Hiroshi Otani
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Correspondence to Nigel J. Mouncey.

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This article is part of the Special Issue “Natural Product Discovery and Development in the Genomic Era 2019”.

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Mouncey, N.J., Otani, H., Udwary, D. et al. New voyages to explore the natural product galaxy. J Ind Microbiol Biotechnol 46, 273–279 (2019). https://doi.org/10.1007/s10295-018-02122-w

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