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

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Abstract

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 Ca 2+ to cooperatively control the stereochemistry of hapalindole natural products.

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europepmc
last seen: 2026-05-19T01:45:01.086888+00:00