Enzymatic one-step ring contraction for quinolone biosynthesis

Nat Commun. 2018 Jul 19;9(1):2826. doi: 10.1038/s41467-018-05221-5.

Abstract

The 6,6-quinolone scaffolds on which viridicatin-type fungal alkaloids are built are frequently found in metabolites that display useful biological activities. Here we report in vitro and computational analyses leading to the discovery of a hemocyanin-like protein AsqI from the Aspergillus nidulans aspoquinolone biosynthetic pathway that forms viridicatins via a conversion of the cyclopenin-type 6,7-bicyclic system into the viridicatin-type 6,6-bicyclic core through elimination of carbon dioxide and methylamine through methyl isocyanate.

Publication types

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

MeSH terms

  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Aspergillus nidulans / chemistry
  • Aspergillus nidulans / genetics
  • Aspergillus nidulans / metabolism*
  • Binding Sites
  • Biosynthetic Pathways
  • Carbon Dioxide / chemistry
  • Carbon Dioxide / metabolism
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Cyclization
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Hemocyanins / chemistry
  • Hemocyanins / genetics
  • Hemocyanins / metabolism*
  • Hydroxyquinolines / chemistry
  • Hydroxyquinolines / metabolism
  • Isocyanates / chemistry
  • Isocyanates / metabolism
  • Kinetics
  • Methylamines / chemistry
  • Methylamines / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Interaction Domains and Motifs
  • Quinolones / chemistry
  • Quinolones / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Zinc / chemistry*
  • Zinc / metabolism

Substances

  • Alkaloids
  • Fungal Proteins
  • Hydroxyquinolines
  • Isocyanates
  • Methylamines
  • Quinolones
  • Recombinant Proteins
  • Carbon Dioxide
  • viridicatin
  • Hemocyanins
  • methylamine
  • methyl isocyanate
  • Zinc