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

preprint
submitted on 24.10.2019 and posted on 25.10.2019 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.

Funding

R35 GM118101

CHE- 1700982

P01 CA125066

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

No conflict of interest

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