Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids. Academic Article uri icon


  • 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-(14)C]-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.

published proceedings

  • Chem Biol

author list (cited authors)

  • Morbidoni, H. R., Vilchze, C., Kremer, L., Bittman, R., Sacchettini, J. C., & Jacobs, W. R.

citation count

  • 45

complete list of authors

  • Morbidoni, Hector R||Vilch├Ęze, Catherine||Kremer, Laurent||Bittman, Robert||Sacchettini, James C||Jacobs, William R

publication date

  • March 2006