title: Cytochrome P450 OxyBtei catalyzes the first phenolic coupling step in teicoplanin biosynthesis.
abstract: Bacterial cytochrome P450s form a remarkable clade of the P450 superfamily of oxidative hemoproteins, and are often involved in the biosynthesis of complex natural products. Those in a subgroup known as "Oxy enzymes" play a crucial role in the biosynthesis of glycopeptide antibiotics, including vancomycin and teicoplanin. The Oxy enzymes catalyze crosslinking of aromatic residues in the non-ribosomal antibiotic precursor peptide while it remains bound to the non-ribosomal peptide synthetase (NRPS); this crosslinking secures the three-dimensional structure of the glycopeptide, crucial for antibiotic activity. We have characterized OxyBtei , the first of the Oxy enzymes in teicoplanin biosynthesis. Our results reveal that OxyBtei possesses a structure similar to those of other Oxy proteins and is active in crosslinking NRPS-bound peptide substrates. However, OxyBtei displays a significantly altered activity spectrum against peptide substrates compared to its well-studied vancomycin homologue.
authors.affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany).
authors.forename: Kristina
authors.initials: K
authors.lastname: Haslinger
authors.forename: Egle
authors.initials: E
authors.lastname: Maximowitsch
authors.forename: Clara
authors.initials: C
authors.lastname: Brieke
authors.forename: Alexa
authors.initials: A
authors.lastname: Koch
authors.forename: Max J
authors.initials: MJ
authors.lastname: Cryle
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D008848:Micromonosporaceae / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D017334:Teicoplanin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010636:Phenols; D017334:Teicoplanin; D003577:Cytochrome P-450 Enzyme System
keywords: biocatalysis; cytochromes; peptide biosynthesis; secondary metabolism; teicoplanin