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Control of Stereoselectivity in Diverse Hapalindole Metabolites Is Mediated by Cofactor Induced Combinatorial Pairing of Stig Cyclases

submitted on 24.10.2019, 00:57 and posted on 25.10.2019, 20:28 by Shasha Li, Sean A. Newmister, andrew n. lowell, Jiachen Zi, Callie R. Chappell, Fengan Yu, Robert M. Hohlman, Jimmy Orjala, Robert M. Williams, David H. Sherman

The stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by the Stig cyclases through a three-step cascade involving Cope rearrangement, 6-exo-trig cyclization and a final electrophilic aromatic substitution. Here we report a comprehensive study of all currently annotated Stig cyclases, and reveal that these proteins can assemble into heteromeric complexes induced by Ca2+ to cooperatively control the stereochemistry of hapalindole natural products.


R35 GM118101

CHE- 1700982

P01 CA125066


Email Address of Submitting Author


University of Michigan


United States

ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest