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

Angew Chem Int Ed Engl. 2020 May 18;59(21):8166-8172. doi: 10.1002/anie.201913686. Epub 2020 Mar 19.

Abstract

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.

Keywords: biocatalysis; cyclases; indoles; oligomerization; rearrangements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / metabolism*
  • Calcium / chemistry
  • Cyanobacteria / enzymology
  • Cyclization
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / metabolism
  • Indoles / chemistry*
  • Indoles / metabolism
  • Lyases / metabolism*
  • Stereoisomerism

Substances

  • Bacterial Proteins
  • Indole Alkaloids
  • Indoles
  • hapalindole U
  • Lyases
  • Calcium

Supplementary concepts

  • Fischerella ambigua