Roles of VioG and VioQ in the incorporation and modification of the capreomycidine residue in the peptide antibiotic viomycin

Xiaobo Fei, Xihou Yin, Ling Zhang, T. Mark Zabriskie

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single-module peptide synthetase from the viomycin gene cluster cloned from Streptomyces vinaceus (ATCC11861), specifically activates capreomycidine for incorporation into viomycin (tuberactinomycin B). Insertional disruption of the putative hydroxylase gene vioQ resulted in a mutant that accumulated tuberactinomycin O, suggesting that hydroxylation at C-5 of the capreomycidine residue is a post-assembly event. The inactivated chromosomal copy of vioQ could be complemented with a wild-type copy of the gene to restore viomycin production.

Original languageEnglish (US)
Pages (from-to)618-622
Number of pages5
JournalJournal of Natural Products
Volume70
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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