Flavoproteins catalyse a diversity of fundamental redox reactions and are one of the most studied enzyme families. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate. Here we report that the bacterial flavoenzyme EncM catalyses the peroxyflavin- independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics and isotope labelling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unexpected stable flavin-oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization. © 2013 Macmillan Publishers Limited. All rights reserved.
CITATION STYLE
Teufel, R., Miyanaga, A., Michaudel, Q., Stull, F., Louie, G., Noel, J. P., … Moore, B. S. (2013). Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Nature, 503(7477), 552–556. https://doi.org/10.1038/nature12643
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