FasR, a novel class of transcriptional regulator, governs the activation of fatty acid biosynthesis genes in Streptomyces coelicolor.

ARABOLAZA A,; DANGELO, M; COMBA, S; GRAMAJO, H

MOLECULAR MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2010 p. 47 - 63

0950-382X

Membrane lipid homeostasis is essential for bacterial survival and adaptation to different environments. The regulation of fatty acid biosynthesis is therefore crucial for maintaining the correct composition and biophysical properties of cell membranes. This regulation occurs at several levels, including the transcriptional regulation of genes involved in lipid metabolism. In Streptomyces coelicolor we found that the control of lipid homeostasis is accomplished, at least in part, through the transcriptional regulation of fatty acid biosynthetic genes. A novel transcription factor, FasR (SCO2386), controls expression of the fabDHPF operon and lies immediately upstream of fabD, in a cluster of genes that is highly conserved within actinomycetes. Disruption of fasR resulted in a mutant strain, with severe growth defects and a delay in the timing of morphological and physiological differentiation. Expression of fab genes was down-regulated in the fasR mutant, indicating a role for this transcription factor as an activator. Consequently, the mutant showed a significant drop in fatty acid synthase activity, and alterations in membrane lipid composition and triacylglyceride accumulation. FasR binds specifically to a DNA sequence containing the fabDHPF promoter region, both in vivo and in vitro. These data provide the first example of positive regulation of fatty acid biosynthesis in nature.