Polyketide intermediate mimics as probes for revealing cryptic stereochemistry of ketoreductase domains.

ABSTRACT: Among natural product families, polyketides have shown the most promise for combinatorial biosynthesis of natural product-like libraries. Though recent research in the area has provided many mechanistic revelations, a basic-level understanding of kinetic and substrate tolerability is still needed before the full potential of combinatorial biosynthesis can be realized. We have developed a novel set of chemical probes for the study of ketoreductase domains of polyketide synthases. This chemical tool-based approach was validated using the ketoreductase of pikromycin module 2 (PikKR2) as a model system. Triketide substrate mimics 12 and 13 were designed to increase stability (incorporating a nonhydrolyzable thioether linkage) and minimize nonessential functionality (truncating the phosphopante

SUBMITTER: Li Y 

PROVIDER: S-EPMC4273979 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature