Mycolic acids are alpha-alkyl, beta-hydroxy long-chain fatty acids, which are essential components of the cell walls of mycobacteria and related bacteria such as Nocardia and Rhodococcus. The structures of mycolic acids are composed of a meromycolic chain and an alpha-branch. Functional groups and carbon chain lengths vary depending on the genus, species and strain levels of bacteria. Corynebacteria also synthesize mycolic acids, called corynomycolic acids, which are shorter and less modified than mycobacterial mycolic acids. In mycobacteria, the biosynthetic pathway starts with de novo synthesis and elongation of fatty acids by FAS I and FAS II, respectively. FAS II products undergo further elongation, desaturation and modification to produce meromycolic acids, while carboxylation of very-long-chain acyl-CoA further elongated by FAS I yields carboxyacyl-CoA (alpha-branch). Mycolic beta-ketoester formed by condensation of the activated meromycolic chain and the carboxylated acyl chain, upon reduction, leads to the mature mycolate, TMM (trehalose monomycolate). Mycolyltransferase (Ag85) then catalyzes the transfer of a mycolate from TMM to the cell wall arabinogalactan and to other TMMs to form mAGP and TDM (trehalose dimycolate), respectively.
Di Capua CB, Belardinelli JM, Carignano HA, Buchieri MV, Suarez CA, Morbidoni HR
Title
Unveiling the Biosynthetic Pathway for Short Mycolic Acids in Nontuberculous Mycobacteria: Mycobacterium smegmatis MSMEG_4301 and Its Ortholog Mycobacterium abscessus MAB_1915 Are Essential for the Synthesis of alpha'-Mycolic Acids.
Lefebvre C, Frigui W, Slama N, Lauzeral-Vizcaino F, Constant P, Lemassu A, Parish T, Eynard N, Daffe M, Brosch R, Quemard A
Title
Discovery of a novel dehydratase of the fatty acid synthase type II critical for ketomycolic acid biosynthesis and virulence of Mycobacterium tuberculosis.
Bories P, Rima J, Tranier S, Marcoux J, Grimoire Y, Tomaszczyk M, Launay A, Fata K, Marrakchi H, Burlet-Schiltz O, Mourey L, Ducoux-Petit M, Bardou F, Bon C, Quemard A
Title
HadBD dehydratase from Mycobacterium tuberculosis fatty acid synthase type II: A singular structure for a unique function.
Puech V, Guilhot C, Perez E, Tropis M, Armitige LY, Gicquel B, Daffe M
Title
Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis.
Jackson M, Raynaud C, Laneelle MA, Guilhot C, Laurent-Winter C, Ensergueix D, Gicquel B, Daffe M
Title
Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope.
Laval F, Haites R, Movahedzadeh F, Lemassu A, Wong CY, Stoker N, Billman-Jacobe H, Daffe M
Title
Investigating the function of the putative mycolic acid methyltransferase UmaA: divergence between the Mycobacterium smegmatis and Mycobacterium tuberculosis proteins.
Gande R, Gibson KJ, Brown AK, Krumbach K, Dover LG, Sahm H, Shioyama S, Oikawa T, Besra GS, Eggeling L
Title
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.
