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Abyssomicin Biosynthesis: Formation of an Unusual Polyketide, Antibiotic-Feeding Studies and Genetic Analysis

Lookup NU author(s): Dr Gabriel Uguru, Dr James Stach

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Abstract

Abyssomicin C, produced by the marine actinomycete Verrucosispora sp. AB-18-032, is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and inhibits p-aminobenzoate formation during tetrahydrofolate synthesis, the first natural product active against this therapeutic target. To investigate the biosynthesis of this small but structurally complex secondary metabolite, we carried out feeding studies using 13C labeled polyketide building blocks. Formation of abyssomicin C requires two propionates, five acetates and one glucose-derived metabolite. Identification and sequencing of the abyssomicin biosynthetic gene cluster revealed a 57 kb segment of Verrucosispora sp. AB-18-032 DNA that contained all of the genes necessary for abyssomicin biosynthesis. The identity of the biosynthetic gene cluster was confirmed by gene inactivation and complementation experiments (the first genetic manipulation of a member of this genus), and a model for abyssomicin C biosynthesis is proposed


Publication metadata

Author(s): Gottardi EM, Krawczyk JM, von Suchodoletz H, Schadt S, Mühlenweg A, Uguru GC, Pelzer S, Fiedler H-P, Bibb MJ, Stach JEM, Süssmuth RD

Publication type: Article

Publication status: Published

Journal: ChemBioChem

Year: 2011

Volume: 12

Issue: 9

Pages: 1401-1410

Print publication date: 09/06/2011

ISSN (print): 1439-4227

ISSN (electronic): 1439-7633

Publisher: Wiley - VCH Verlag GmbH & Co. KGaA

URL: http://dx.doi.org/10.1002/cbic.201100172

DOI: 10.1002/cbic.201100172


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