Transcriptional regulation of fatty acid biosynthesis in Streptomyces coelicolor

ARABOLAZA, ANA; COMBA, SANTIAGO; GRAMAJO, HUGO

Puerto Vallarta

Simposio; 16th International Symposium on the Biology of Actinomycetes; 2011

ISBA

Membrane lipid homeostasis is of critical importance to bacterial cell physiology. Fatty Acids (FA) and their derivatives are essential structural components of bacterial membranes and their biosynthesis represents one of the most energetically expensive processes to the cell. Thus, microorganisms have evolved sophisticated mechanisms to finely control expression of genes responsible for the formation and degradation of FA. In Streptomyces coelicolor, genes encoding core proteins of the Fatty Acid Synthase complex (FAS) are clustered at a single locus forming a four genes operon (fabDHPF). Bioinformatic analysis of this genome region revealed the presence of a highly conserved open reading frame containing the characteristic HTH motif present in transcriptional regulators, the putative protein was called FasR. Here, we present the in vivo and in vitro characterization of FasR, the first member of a new family of transcriptional regulators that controls the transcription of the fab operon in S. coelicolor. A FasR mutant was constructed and the strain thoroughly characterized at the physiological level. The mutant presented diminished FAS activity, altered FA composition and reduced triacylglyceride content in comparison with the wild type M145 strain. Biophysical and biochemical studies suggested that FasR activity is regulated by the levels of malonyl-CoA. Altogether, these studies consistently showed that FasR is an activator of the fatty acid biosynthesis genes whose presence is essential for this bacterium to have a normal morphological and physiological differentiation. Overall, we propose that S. coelicolor has the ability to maintain lipid homeostasis by sensing the malonyl-CoA pool and responding to it by adjusting expression of the fabDHPF genes via a FasR-mediated regulation.