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One‐Pot Enzymatic Synthesis of Merochlorin A and B
Author(s) -
Teufel Robin,
Kaysser Leonard,
Villaume Matthew T.,
Diethelm Stefan,
Carbullido Mary K.,
Baran Phil S.,
Moore Bradley S.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201405694
Subject(s) - polyketide , prenylation , prenyltransferase , polyketide synthase , chemistry , stereochemistry , biosynthesis , moiety , enzyme , streptomyces , atp synthase , biochemistry , terpene , chemical synthesis , bacteria , in vitro , biology , genetics
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.