title: Aminoacyl-coenzyme A synthesis catalyzed by a CoA ligase from Penicillium chrysogenum.
abstract: Coenzyme A ligases play an important role in metabolism by catalyzing the activation of carboxylic acids. In this study we describe the synthesis of aminoacyl-coenzyme As (CoAs) catalyzed by a CoA ligase from Penicillium chrysogenum. The enzyme accepted medium-chain length fatty acids as the best substrates, but the proteinogenic amino acids L-phenylalanine and L-tyrosine, as well as the non-proteinogenic amino acids D-phenylalanine, D-tyrosine and (R)- and (S)-β-phenylalanine were also accepted. Of these amino acids, the highest activity was found for (R)-β-phenylalanine, forming (R)-β-phenylalanyl-CoA. Homology modeling suggested that alanine 312 is part of the active site cavity, and mutagenesis (A312G) yielded a variant that has an enhanced catalytic efficiency with β-phenylalanines and D-α-phenylalanine.
authors.affiliation: Biochemical Laboratory, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, Groningen NL-9747 AG, The Netherlands.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Koetsier
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jekel
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Wijma
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Dick B
authors.initials: DB
authors.lastname: Janssen
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D055162:Biocatalysis; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism; D003065:Coenzyme A / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010408:Penicillium chrysogenum / Q000201:enzymology* / Q000235:genetics; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D005656:Fungal Proteins; D014443:Tyrosine; D010649:Phenylalanine; D003066:Coenzyme A Ligases; D003065:Coenzyme A