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Diversifying microbial natural products for drug discovery

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Abstract

Historically, nature has provided the source for the majority of the drugs in use today. More than 20,000 microbial secondary metabolites have been described, but only a small percentage of these have been carried forward as natural product drugs. Natural products are in tough competition with large chemical libraries and with combinatorial chemistries. Hence, each step of a natural product program has to be more efficient than ever, starting from the collection of environmental samples and the selection of strains, to metabolic expression, genetic exploitation, sample preparation and chemical dereplication. This review will focus on approaches for diversifying microbial natural product strains and extract libraries, while decreasing genetic and chemical redundancy.

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Acknowledgements

The authors would like to thank Drs. Andy Staley, Xiaoyu Shen, Eugenie Boutin, Hyedong Yoo, Alexei Belenky, Bill Pierceall, Baoliang Cui and Shuhui Chen for critical reading and comments on the manuscript. Additional gratitude is extended to the drug discovery teams at Cetek, Inc.

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  1. Cetek Corporation, 260 Cedar Hill St., Marlborough, MA 01752, USA

    V. Knight, J.-J. Sanglier, D. DiTullio, S. Braccili, P. Bonner, J. Waters, D. Hughes & L. Zhang

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  1. V. Knight
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Correspondence to L. Zhang.

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V. Knight and J.-J. Sanglier contributed equally to this work

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Knight, V., Sanglier, JJ., DiTullio, D. et al. Diversifying microbial natural products for drug discovery. Appl Microbiol Biotechnol 62, 446–458 (2003). https://doi.org/10.1007/s00253-003-1381-9

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