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Cytochrome P450 OxyB tei Catalyzes the First Phenolic Coupling Step in Teicoplanin Biosynthesis
Author(s) -
Haslinger Kristina,
Maximowitsch Egle,
Brieke Clara,
Koch Alexa,
Cryle Max J.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402441
Subject(s) - biosynthesis , chemistry , teicoplanin , coupling (piping) , cytochrome p450 , biochemistry , stereochemistry , combinatorial chemistry , biology , metabolism , enzyme , genetics , bacteria , materials science , vancomycin , staphylococcus aureus , metallurgy
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 OxyB tei , the first of the Oxy enzymes in teicoplanin biosynthesis. Our results reveal that OxyB tei possesses a structure similar to those of other Oxy proteins and is active in crosslinking NRPS‐bound peptide substrates. However, OxyB tei displays a significantly altered activity spectrum against peptide substrates compared to its well‐studied vancomycin homologue.