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

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  2. Dr Gabriel Uguru
  3. Dr James Stach
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
JournalChemBioChem
Year2011
Volume12
Issue9
Pages1401-1410
ISSN (print)1439-4227
ISSN (electronic)1439-7633
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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
PublisherWiley - VCH Verlag GmbH & Co. KGaA
URLhttp://dx.doi.org/10.1002/cbic.201100172
DOI10.1002/cbic.201100172
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