An Oxetane-Based Polyketide Surrogate To Probe Substrate Binding in a Polyketide Synthase.

ABSTRACT: Polyketides are a large class of bioactive natural products with a wide range of structures and functions. Polyketides are biosynthesized by large, multidomain enzyme complexes termed polyketide synthases (PKSs). One of the primary challenges when studying PKSs is the high reactivity of their poly-β-ketone substrates. This has hampered structural and mechanistic characterization of PKS-polyketide complexes, and, as a result, little is known about how PKSs position the unstable substrates for proper catalysis while displaying high levels of regio- and stereospecificity. As a first step toward a general plan to use oxetanes as carbonyl isosteres to broadly interrogate PKS chemistry, we describe the development and application of an oxetane-based PKS substrate mimic. This enabled the first st

SUBMITTER: Ellis BD 

PROVIDER: S-EPMC6625825 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature