Characterization of Mycobacterium smegmatis Expressing the Mycobacterium tuberculosis Fatty Acid Synthase I (fas1) Gene

AUTOR(ES)

Zimhony, Oren

FONTE

American Society for Microbiology

RESUMO

Unlike most other bacteria, mycobacteria make fatty acids with the multidomain enzyme eukaryote-like fatty acid synthase I (FASI). Previous studies have demonstrated that the tuberculosis drug pyrazinamide and 5-chloro-pyrazinamide target FASI activity. Biochemical studies have revealed that in addition to C16:0, Mycobacterium tuberculosis FASI synthesizes C26:0 fatty acid, while the Mycobacterium smegmatis enzyme makes C24:0 fatty acid. In order to express M. tuberculosis FASI in a rapidly growing Mycobacterium and to characterize the M. tuberculosis FASI in vivo, we constructed an M. smegmatis Δfas1 strain which contained the M. tuberculosis fas1 homologue. The M. smegmatis Δfas1 (attB::M. tuberculosis fas1) strain grew more slowly than the parental M. smegmatis strain and was more susceptible to 5-chloro-pyrazinamide. Surprisingly, while the M. smegmatis Δfas1 (attB::M. tuberculosis fas1) strain produced C26:0, it predominantly produced C24:0. These results suggest that the fatty acid elongation that produces C24:0 or C26:0 in vivo is due to a complex interaction among FASI, FabH, and FASII and possibly other systems and is not solely due to FASI elongation, as previously suggested by in vitro studies.

Documentos Relacionados

• Genetic Analysis of Hybrid Strains Trisomic for the Chromosome Containing a Fatty Acid Synthetase Gene Complex (fas1) in Yeast
• A downstream regulatory element located within the coding sequence mediates autoregulated expression of the yeast fatty acid synthase gene FAS2 by the FAS1 gene product
• Characterization of the mIHF Gene of Mycobacterium smegmatis
• The RD1 virulence locus of Mycobacterium tuberculosis regulates DNA transfer in Mycobacterium smegmatis
• Fatty acid biosynthesis in Mycobacterium tuberculosis: Lateral gene transfer, adaptive evolution, and gene duplication