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

32 Citations (Scopus)

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

Fingerprint

Biosynthesis
Mycobacterium smegmatis
Fatty Acids
Degradation
Acids
Mycolic Acids
Mycobacterium bovis
Poisons
Corrosion inhibitors
Mycobacterium
Metabolites
2-hexadecynoic acid

Keywords

  • CHEMBIO
  • MICROBIO

ASJC Scopus subject areas

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

Cite this

Dual Inhibition of Mycobacterial Fatty Acid Biosynthesis and Degradation by 2-Alkynoic Acids. / Morbidoni, Hector R.; Vilchèze, Catherine; Kremer, Laurent; Bittman, Robert; Sacchettini, James C.; Jacobs, William R.

In: Chemistry and Biology, Vol. 13, No. 3, 01.03.2006, p. 297-307.

Research output: Contribution to journalArticle

Morbidoni, Hector R. ; Vilchèze, Catherine ; Kremer, Laurent ; Bittman, Robert ; Sacchettini, James C. ; Jacobs, William R. / Dual Inhibition of Mycobacterial Fatty Acid Biosynthesis and Degradation by 2-Alkynoic Acids. In: Chemistry and Biology. 2006 ; Vol. 13, No. 3. pp. 297-307.
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