Cytochrome P450 OxyBtei catalyzes the first phenolic coupling step in teicoplanin biosynthesis

Chembiochem. 2014 Dec 15;15(18):2719-28. doi: 10.1002/cbic.201402441. Epub 2014 Oct 30.

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.

Keywords: biocatalysis; cytochromes; peptide biosynthesis; secondary metabolism; teicoplanin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biocatalysis
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Micromonosporaceae / chemistry
  • Micromonosporaceae / metabolism*
  • Models, Molecular
  • Phenols / chemistry
  • Phenols / metabolism*
  • Teicoplanin / chemistry
  • Teicoplanin / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Phenols
  • Teicoplanin
  • Cytochrome P-450 Enzyme System