Dual Inhibition of Mycobacterial Fatty Acid Biosynthesis and Degradation by 2-Alkynoic Acids

Hector R. Morbidoni, Catherine Vilchèze, Laurent Kremer, Robert Bittman, James C. Sacchettini, William R. Jacobs

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against Mycobacterium smegmatis and Mycobacterium bovis BCG. At subinhibitory concentrations, M. smegmatis rapidly transformed [1-14C]-2-hexadecynoic acid into endogenous fatty acids and elongated them into mycolic acids. Toxic concentrations of 2-hexadecynoic acid resulted in accumulation of 3-ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic acid, an inhibitor of fatty acid degradation. The combination of these two metabolites is necessary to achieve the inhibition of M. smegmatis. We conclude that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty acid biosynthesis, and fatty acid degradation, pathways of significant importance for mycobacteria.

Original languageEnglish (US)
Pages (from-to)297-307
Number of pages11
JournalChemistry and Biology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2006

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Keywords

  • CHEMBIO
  • MICROBIO

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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