Control of Stereoselectivity in Diverse Hapalindole Metabolites is Mediated by Cofactor-Induced Combinatorial Pairing of Stig Cyclases.

Shasha LiSean A NewmisterAndrew N LowellJiachen ZiCallie R ChappellFengan YuRobert M HohlmanJimmy OrjalaRobert M WilliamsDavid H Sherman

Published in: Angewandte Chemie (International ed. in English) (2020)

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

Keyphrases

high glucose
ms ms
diabetic rats
oxidative stress
protein kinase