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Harnessing natural product assembly lines: structure, promiscuity, and engineering

  • Metabolic Engineering and Synthetic Biology
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.

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Acknowledgments

Research on natural product chemical and synthetic biology in our lab is supported by a National Science Foundation CAREER Award (CHE-1151299) and NIH Grant 1R01GM104258-01. The authors would like to thank Edward Kalkreuter for critically reading this manuscript.

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Correspondence to Gavin J. Williams.

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Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

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Ladner, C.C., Williams, G.J. Harnessing natural product assembly lines: structure, promiscuity, and engineering. J Ind Microbiol Biotechnol 43, 371–387 (2016). https://doi.org/10.1007/s10295-015-1704-8

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