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

Metabolic Engineering and Synthetic Biology


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.


Combinatorial biosynthesis Synthetic biology Enzyme engineering Polyketide synthases Non-ribosomal peptide synthases 



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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© Society for Industrial Microbiology and Biotechnology 2015

Authors and Affiliations

  1. 1.Department of ChemistryNC State UniversityRaleighUSA

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