title: The two carboxylases of Corynebacterium glutamicum essential for fatty acid and mycolic acid synthesis.
abstract: The suborder Corynebacterianeae comprises bacteria like Mycobacterium tuberculosis and Corynebacterium glutamicum, and these bacteria contain in addition to the linear fatty acids, unique alpha-branched beta-hydroxy fatty acids, called mycolic acids. Whereas acetyl-coenzyme A (CoA) carboxylase activity is required to provide malonyl-CoA for fatty acid synthesis, a new type of carboxylase is apparently additionally present in these bacteria. It activates the alpha-carbon of a linear fatty acid by carboxylation, thus enabling its decarboxylative condensation with a second fatty acid to afford mycolic acid synthesis. We now show that the acetyl-CoA carboxylase of C. glutamicum consists of the biotinylated alpha-subunit AccBC, the beta-subunit AccD1, and the small peptide AccE of 8.9 kDa, forming an active complex of approximately 812,000 Da. The carboxylase involved in mycolic acid synthesis is made up of the two highly similar beta-subunits AccD2 and AccD3 and of AccBC and AccE, the latter two identical to the subunits of the acetyl-CoA carboxylase complex. Since AccD2 and AccD3 orthologues are present in all Corynebacterianeae, these polypeptides are vital for mycolic acid synthesis forming the unique hydrophobic outer layer of these bacteria, and we speculate that the two beta-subunits present serve to lend specificity to this unique large multienzyme complex.
authors.affiliation: Institute for Biotechnology, Research Centre Juelich, D-52425 Juelich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Gande
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Dover
authors.forename: Karin
authors.initials: K
authors.lastname: Krumbach
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Hermann
authors.initials: H
authors.lastname: Sahm
authors.forename: Tadao
authors.initials: T
authors.lastname: Oikawa
authors.forename: Lothar
authors.initials: L
authors.lastname: Eggeling
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis / Q000187:drug effects; D002951:Citrates / Q000494:pharmacology; D048230:Corynebacterium glutamicum / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005971:Glutamates / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008957:Models, Genetic; D008970:Molecular Weight; D009171:Mycolic Acids / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D002951:Citrates; D005227:Fatty Acids; D005971:Glutamates; D007527:Isoenzymes; D009171:Mycolic Acids; D021122:Protein Subunits; D000103:Acetyl-CoA Carboxylase