title: The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved in formation of the peptidoglycan biosynthesis inhibitor mersacidin.
abstract: The lantibiotic mersacidin inhibits peptidoglycan biosynthesis by binding to the peptidoglycan precursor lipid II. Mersacidin contains an unsaturated thioether bridge, which is proposed to be synthesized by posttranslational modifications of threonine residue +15 and the COOH-terminal cysteine residue of the mersacidin precursor peptide MrsA. We show that the flavoprotein MrsD catalyzes the oxidative decarboxylation of the COOH-terminal cysteine residue of MrsA to an aminoenethiol residue. MrsD belongs to the recently described family of homo-oligomeric flavin-containing Cys decarboxylases (i.e., the HFCD protein family). Members of this protein family include the bacterial Dfp proteins (which are involved in coenzyme A biosynthesis), eukaryotic salt tolerance proteins, and further oxidative decarboxylases such as EpiD. In contrast to EpiD and Dfp, MrsD is a FAD and not an FMN-dependent flavoprotein. HFCD enzymes are characterized by a conserved His residue which is part of the active site. Exchange of this His residue for Asn led to inactivation of MrsD. The lantibiotic-synthesizing enzymes EpiD and MrsD have different substrate specificities.
authors.affiliation: Mikrobielle Genetik, Auf der Morgenstelle 15, Verfügungsgebäude, Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Majer
authors.forename: Dietmar G
authors.initials: DG
authors.lastname: Schmid
authors.forename: Karsten
authors.initials: K
authors.lastname: Altena
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
authors.forename: Thomas
authors.initials: T
authors.lastname: Kupke
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins; D002262:Carboxy-Lyases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002384:Catalysis; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis*; D011498:Protein Precursors / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D005420:Flavoproteins; D010455:Peptides; D010457:Peptidoglycan; D011498:Protein Precursors; C069959:mersacidin; D010088:Oxidoreductases; C075971:epidermin decarboxylase; D002262:Carboxy-Lyases; C450426:MrsD protein, Bacillus; C024981:cysteine decarboxylase