These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

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

submitted on 02.12.2019, 13:06 and posted on 11.12.2019, 06:26 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.


National Institutes of Health R01CA070375

National Institutes of Health R35 GM118101

Hans W. Vahlteich Professorship

Rackham Predoctoral Fellowship


Email Address of Submitting Author


University of Michigan


United States

ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no conflict of interest