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.
Control of Stereoselectivity in Diverse Hapalindole Metabolites Is Mediated by Cofactor Induced Combinatorial Pairing of Stig Cyclases
25 October 2019, Version 1
ChemRxiv SI 20191023