One‐Pot Enzymatic Synthesis of Merochlorin A and B |
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| Authors: | Dr. Robin Teufel Dr. Leonard Kaysser Matthew T. Villaume Dr. Stefan Diethelm Mary K. Carbullido Prof. Dr. Phil S. Baran Prof. Dr. Bradley S. Moore |
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| Affiliation: | 1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037 (USA) http://scrippsscholars.ucsd.edu/bsmoore;2. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037 (USA);3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093 (USA) |
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| Abstract: | The polycycles merochlorin A and B are complex halogenated meroterpenoid natural products with significant antibacterial activities and are produced by the marine bacterium Streptomyces sp. strain CNH‐189. Heterologously produced enzymes and chemical synthesis are employed herein to fully reconstitute the merochlorin biosynthesis in vitro. The interplay of a dedicated type III polyketide synthase, a prenyl diphosphate synthase, and an aromatic prenyltransferase allow formation of a highly unusual aromatic polyketide‐terpene hybrid intermediate which features an unprecedented branched sesquiterpene moiety from isosesquilavandulyl diphosphate. As supported by in vivo experiments, this precursor is furthermore chlorinated and cyclized to merochlorin A and isomeric merochlorin B by a single vanadium‐dependent haloperoxidase, thus completing the remarkably efficient pathway. |
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| Keywords: | biosynthesis enzyme catalysis natural products polyketides terpenoids |
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