S113 A Carbonate-forming Baeyer-Villiger Monooxygenase in the Biosynthesis of Cytochalasin E
Wednesday, July 23, 2014: 11:00 AM
Regency Ballroom B, Second Floor (St. Louis Hyatt Regency at the Arch)
Youcai Hu1, Wei Xu1, Jingjing Wang1, Wen-Bing Yin1, Kangjian Qiao1, Yi Tang1 and David Dietrich2, (1)Department of Chemical and Biomolecular Engineering,, University of California Los Angeles, Los Angeles, CA, (2)Department of Chemistry, University of Alberta, Edmonton, Canada
Despite the remarkable versatility displayed by flavin-dependent monooxygeneases (FMOs) in natural product

biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. This is a

challenging synthetic transformation of which only few examples exist. Here we report a remarkable multifunctional

Baeyer-Villiger monooxygenase CcsB, which catalyzes the formation of an in-line carbonate in the macrocyclic

portion of the potent angiogenesis inhibitor cytochalasin E. We demonstrate that while CcsB inserts the first oxygen

into the ketone-containing substrate via a Baeyer-Villiger mechanism, insertion of the second oxygen to form

carbonate relies on the arrangement of the neighboring vinylogous, 1,5-diketone. Insights from this study not only

expand the repertoire of activities of FMOs, but also provide a possible synthetic strategy for transformation of

ketones into carbonates.