Abstract 2802 Bisepoxide formation by a flavin-dependent monooxygenase during lasalocid A biosynthesis

Lasalocid A is a prototypical polyether natural product. A key step in lasalocid A biosynthesis is the transformation of a polyene polyketide intermediate into an (R,R),(R,R) bisepoxide by the flavin-dependent monooxygenase Lsd18. The goal of our study is to determine how Lsd18 catalyzes the enantioselective epoxidation of two different C=C groups in the polyene substrate. We determined the X-ray crystal structure of Lsd18 by itself, Lsd18 in complex with a diene substrate analog, and Lsd18 in complex with a bisepoxide product analog.