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

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-(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.

authors

• Sacchettini, James

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||Vilchèze, Catherine||Kremer, Laurent||Bittman, Robert||Sacchettini, James C||Jacobs, William R

publication date

• March 2006

publisher

• Elsevier  Publisher

published in

• Chemistry and Biology  Journal

keywords

• Alkynes
• Anti-Bacterial Agents
• Fatty Acids
• Fatty Acids, Unsaturated
• Models, Chemical
• Mycobacterium
• Mycobacterium Bovis
• Mycobacterium Smegmatis
• Mycolic Acids

PubMed Central ID

• 16638535

Digital Object Identifier (DOI)

• 10.1016/j.chembiol.2006.01.005

start page

• 297

end page

• 307

volume

• 13

issue

• 3

URL

• http://dx.doi.org/10.1016/j.chembiol.2006.01.005