Components and Key Regulatory Steps of Lipid Biosynthesis in Actinomycetes
The biochemical steps in fatty acid synthesis are highly conserved in bacteria and in most organisms. However, the data provided by the massive genomic sequencing revealed a surprising amount of diversity in the genes, enzymes, and genetic organization of the components responsible for bacterial lipid synthesis, with these differences being even more striking in the order Actinomycetales. Fatty acid biosynthesis is energetically very expensive for the cell; therefore, adjusting the rate of fatty acid synthesis, in order to maintain membrane lipid homeostasis, is a key factor for bacterial survival. Bacteria have evolved sophisticated and diverse mechanisms to finely control the expression of the genes responsible for the synthesis of fatty acids and, in some cases, also by regulating the activity of the pacemaker enzymes. In this chapter we summarize the main components of fatty acid biosynthesis and their regulation in different genera of actinomycetes, highlighting the main differences found between them and also with other bacteria. The main focus has been put into the acyl-CoA carboxylases, the fatty acid synthases, and on the regulatory elements that control these pathways.
This work was supported by NIH (1R01AI095183-01), ANPCyT PICT-2012-0168, PICT 2015-2022 and PID-2013-0042 to HG, PICT 2015-0796 to GG, PICT 2013-1981 to AA, and PICT 2014-1454 to LD.
- Blanchard CZ, Chapman-Smith A, Wallace JC, Waldrop GL (1999) The biotin domain peptide from the biotin carboxyl carrier protein of Escherichia coli acetyl-CoA carboxylase causes a marked increase in the catalytic efficiency of biotin carboxylase and carboxyltransferase relative to free biotin. J Biol Chem 274:31767–31769PubMedCrossRefPubMedCentralGoogle Scholar
- Chopra T, Gokhale RS (2009) Polyketide versatility in the biosynthesis of complex mycobacterial cell wall lipids. Methods Enzymol 459:259–94.Google Scholar
- Gande R, Gibson KJC, Brown AK et al (2004) Acyl-CoA carboxylases (accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycolic acid biosynthesis in Corynebacterianeae such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J Biol Chem 279:44847–44857PubMedCrossRefPubMedCentralGoogle Scholar
- Gastambide O, Lederer E (1960) Biosynthesis of corynomycolic acid from 2 molecules of palmitic acid. Biochem Z 333:285–295Google Scholar
- Rangan V, Smith S (2003) Fatty acid synthesis in eukaryotes. In: Vance D, Vance J (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier, Amsterdam, pp 151–179Google Scholar
- Singh R, Mo S, Florova G, Reynolds KA (2012) Streptomyces coelicolor RedP and FabH enzymes, initiating undecylprodiginine and fatty acid biosynthesis, exhibit distinct acyl-CoA and malonyl-acyl carrier protein substrate specificities. FEMS Microbiol Lett 328:32–38PubMedCrossRefPubMedCentralGoogle Scholar