Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d-Tyr Analogues.

TitleModulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d-Tyr Analogues.
Publication TypeJournal Article
Year of Publication2018
AuthorsOzturk, S, Forneris, CC, Nguy, AKL, Sorensen, EJ, Seyedsayamdost, MR
JournalJ Org Chem
Volume83
Issue13
Pagination7309-7317
Date Published2018 07 06
ISSN1520-6904
KeywordsAnti-Bacterial Agents, Catalysis, Cytochrome P-450 Enzyme System, Substrate Specificity, Tyrosine, Vancomycin
Abstract

We report a general method for synthesizing diverse d-Tyr analogues, one of the constituents of the antibiotic vancomycin, using a Negishi cross-coupling protocol. Several analogues were incorporated into the vancomycin substrate-peptide and reacted with the biosynthetic enzymes OxyB and OxyA, which install the characteristic aromatic cross-links. We find that even small structural perturbations are not accepted by OxyA. The same modifications, however, enhance the catalytic capabilities of OxyB leading to the formation of a new macrocycle within the vancomycin framework.

DOI10.1021/acs.joc.8b00916
Alternate JournalJ. Org. Chem.
PubMed ID29806454