title: One-pot enzymatic synthesis of merochlorin A and B.
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.
authors.affiliation: 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.
authors.forename: Robin
authors.initials: R
authors.lastname: Teufel
authors.forename: Leonard
authors.initials: L
authors.lastname: Kaysser
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Villaume
authors.forename: Stefan
authors.initials: S
authors.lastname: Diethelm
authors.forename: Mary K
authors.initials: MK
authors.lastname: Carbullido
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D003500:Cyclization; D045782:Hemiterpenes / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D054830:Sesterterpenes / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000378:metabolism; D013729:Terpenes / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D054830:Sesterterpenes; D013729:Terpenes; C573231:merochlorin A; C576411:merochlorin B; C004809:isopentenyl pyrophosphate; C043060:3,3-dimethylallyl pyrophosphate
keywords: biosynthesis; enzyme catalysis; natural products; polyketides; terpenoids