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In this work, by using a classical approach for the purification of DNA-binding proteins, we identified FasR, http://www.selleckchem.com/products/Temsirolimus.html a TetR-like transcriptional regulator that specifically binds to the fas promoter region to activate its expression. As demonstrated by RT-PCR, the fas promoter (Pfas) not only transcribes fas but also acpS, two genes that are part of the same transcriptional unit both in M.?smegmatis and in M.?tuberculosis (Fig.?1B and C). acpS codes for a 4-phosphopantetheinyl transferase (PPTase), which transfers the phosphopantetheine group from CoA to the acyl carrier protein (ACP), a key protein involved in lipid biosynthesis (Lambalot et?al., 1996; Walsh et?al., 1997). Chalut et?al. demonstrated that PptT activates the Acp domains of the numerous type-I polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) present in M.?tuberculosis, whereas AcpS is dedicated to the post-translational modification of FAS-I and of the AcpM subunit of FAS-II (Chalut et?al., 2006). Thus, FasR, the regulatory protein of the fas-acpS operon could be considered as a key factor involved in the co-ordination of the activity of the two FAS systems that coexist in mycobacteria. blast analysis, using the amino acid sequence of FasRMT, revealed a significant homology (above 45% of identity along the whole sequence) with other hypothetical proteins present exclusively in actinomycetes, including members of the genera Frankia, Streptomyces, Rhodococcus and Nocardia. Notably, the highest percentages of identity (above 62%) were observed within the FasRMT homologues of the mycolic-acid containing actinomycetes. Since the corresponding genes show a conserved genetic organization compared with that of fasRMT, we propose that they all might share the same physiological role and therefore could be considered orthologues. It is interesting noticing that although Corynebacterium sp. only employs a FAS-I system for the biosynthesis of both fatty acid and corynomycolic acids, our bioinformatic analysis could not find a FasRMT homologue on their genomes, indicating that corynebacteria followed a completely different pathway of evolution for the regulation of this essential metabolism. Recently, a transcriptional regulator of the two fas genes present in Corynebacterium was described (Nickel et?al., 2010). Although this regulatory protein also belongs to the TetR-family of transcriptional regulators, it has no significant homology with fasRMT (