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Gifted microbes for genome mining and natural product discovery

  • Natural Products - Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Actinomycetes are historically important sources for secondary metabolites (SMs) with applications in human medicine, animal health, and plant crop protection. It is now clear that actinomycetes and other microorganisms with large genomes have the capacity to produce many more SMs than was anticipated from standard fermentation studies. Indeed ~90 % of SM gene clusters (SMGCs) predicted from genome sequencing are cryptic under conventional fermentation and analytical analyses. Previous studies have suggested that among the actinomycetes with large genomes, some have the coding capacity to produce many more SMs than others, and that strains with the largest genomes tend to be the most gifted. These contentions have been evaluated more quantitatively by antiSMASH 3.0 analyses of microbial genomes, and the results indicate that many actinomycetes with large genomes are gifted for SM production, encoding 20–50 SMGCs, and devoting 0.8–3.0 Mb of coding capacity to SM production. Several Proteobacteria and Firmacutes with large genomes encode 20–30 SMGCs and devote 0.8–1.3 Mb of DNA to SM production, whereas cultured bacteria and archaea with small genomes devote insignificant coding capacity to SM production. Fully sequenced genomes of uncultured bacteria and archaea have small genomes nearly devoid of SMGCs.

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Acknowledgments

I would like to thank Arny Demain for his unfailing advocacy for natural products spanning many decades, and his many contributions to industrial biotechnology, starting with his seminal publications of cephalosporin C biosynthesis initiated during his tenure at Merck. It has been an honor to know Arny as a friend and mentor, and to contribute to this Special Issue of JIMB celebrating his 90th birthday! I would also like to acknowledge David Hopwood and Satoshi Ōmura and their colleagues for seminal observations on the cryptic secondary metabolite pathways encoded by S. coelicolor and S. avermitilis that have helped catalyze the resurgence of natural product research, particularly the genome mining approach discussed in this article.

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

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