Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement. Academic Article uri icon


  • 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(-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.

published proceedings

  • Nature

altmetric score

  • 5.5

author list (cited authors)

  • Teufel, R., Miyanaga, A., Michaudel, Q., Stull, F., Louie, G., Noel, J. P., ... Moore, B. S.

citation count

  • 140

complete list of authors

  • Teufel, Robin||Miyanaga, Akimasa||Michaudel, Quentin||Stull, Frederick||Louie, Gordon||Noel, Joseph P||Baran, Phil S||Palfey, Bruce||Moore, Bradley S

publication date

  • November 2013

published in