Regulation of fatty acid biosynthesis in mycobacteria

MONDINO S.; SALZMAN V.; GRAMAJO H.; GAGO G.

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

The most relevant lipids in Mycobacterium cell envelope are mycolic acids, unusual fatty acids that are essential for M. tuberculosis survival and virulence. The biosynthetic pathway of these mycolic acids involve two fatty acids synthases (FAS-I and FAS-II) which should be strictly co-regulated to maintain lipid homeostasis in mycobacteria. We discovered a new transcriptional regulator that controls the expression of fasII genes, named MabR. Remarkably, overexpression of MabR in M. smegmatis leads to the transcriptional repression of the fas gene, suggesting that this transcription factor could also be involved in the regulation of FAS-I. However, we could not demonstrate direct binding of MabR to Pfas by EMSA assays. The recently detection of specific DNA-binding activity to Pfas in extracts of M. smegmatis prompted us to seek for a possible new regulator of the fas gene, which could be working in conjunction with MabR to maintain lipid homeostasis in mycobacteria. Purification and future characterization of this protein should help us to elucidate the complex regulatory network of mycolic acids biosynthetic pathway, an attractive target for the development of new antimycobacterial drugs.