One-pot enzymatic synthesis of merochlorin A and B

TitleOne-pot enzymatic synthesis of merochlorin A and B
Publication TypeJournal Article
Year of Publication2014
AuthorsTeufel R., Kaysser L., Villaume M.T, Diethelm S., Carbullido M.K, Baran P.S, Moore BS
JournalAngewandte Chemie-International Edition
Volume53
Pagination11019-11022
Date Published2014/10
Type of ArticleArticle
ISBN Number1433-7851
Accession NumberWOS:000342758200036
Keywordsbiosynthesis; cloning; cyclization; diphosphate; enzyme catalysis; expression; gene-cluster; natural products; pathways; polyketides; synthase; terpenoids
Abstract

The polycycles merochlorinA 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 invitro. The interplay of a dedicated typeIII 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 invivo experiments, this precursor is furthermore chlorinated and cyclized to merochlorinA and isomeric merochlorinB by a single vanadium-dependent haloperoxidase, thus completing the remarkably efficient pathway.

DOI10.1002/anie.201405694
Short TitleAngew. Chem.-Int. Edit.
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Student Publication: 
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