Title | Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d-Tyr Analogues. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Ozturk, S, Forneris, CC, Nguy, AKL, Sorensen, EJ, Seyedsayamdost, MR |
Journal | J Org Chem |
Volume | 83 |
Issue | 13 |
Pagination | 7309-7317 |
Date Published | 2018 07 06 |
ISSN | 1520-6904 |
Keywords | Anti-Bacterial Agents, Catalysis, Cytochrome P-450 Enzyme System, Substrate Specificity, Tyrosine, Vancomycin |
Abstract | <p>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.</p> |
DOI | 10.1021/acs.joc.8b00916 |
Alternate Journal | J Org Chem |
PubMed ID | 29806454 |