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Flavin-Dependent Monooxygenases NotI and NotI′ Mediate Spiro-Oxindole Formation in Biosynthesis of the Notoamides

preprint
submitted on 02.12.2019 and posted on 11.12.2019 by Amy E. Fraley, Hong T. Tran, Ashootosh Tripathi, Sean A. Newmister, Samantha P. Kelly, Hikaru Kato, Sachiko Tsukamoto, Shengying Li, Robert M. Williams, David H. Sherman

The fungal indole alkaloids are a unique class of complex molecules that have a characteristic bicyclo[2.2.2]diazaoctane ring and frequently contain a spiro-oxindole moiety. While various strains produce these compounds, an intriguing case involves the formation of individual antipodes by two unique species of fungi in the generation of the potent anticancer agents (+)- and (-)-notoamide A. NotI and NotI′ have been characterized as flavin-dependent monooxygenases that catalyze epoxidation and semi-Pinacol rearrangement to form the spiro-oxindole center within these molecules. This work elucidates a key step in the biosynthesis of the notoamides and provides an evolutionary hypothesis regarding a common ancestor for production of enantiopure notoamides.

Funding

National Institutes of Health R01CA070375

National Institutes of Health R35 GM118101

Hans W. Vahlteich Professorship

Rackham Predoctoral Fellowship

History

Email Address of Submitting Author

davidhs@umich.edu

Institution

University of Michigan

Country

United States

ORCID For Submitting Author

0000-0001-8334-3647

Declaration of Conflict of Interest

The authors declare no conflict of interest

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