A promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion

Nat Commun. 2018 Jun 27;9(1):2487. doi: 10.1038/s41467-018-04878-2.

Abstract

Microbial aromatic catabolism offers a promising approach to convert lignin, a vast source of renewable carbon, into useful products. Aryl-O-demethylation is an essential biochemical reaction to ultimately catabolize coniferyl and sinapyl lignin-derived aromatic compounds, and is often a key bottleneck for both native and engineered bioconversion pathways. Here, we report the comprehensive characterization of a promiscuous P450 aryl-O-demethylase, consisting of a cytochrome P450 protein from the family CYP255A (GcoA) and a three-domain reductase (GcoB) that together represent a new two-component P450 class. Though originally described as converting guaiacol to catechol, we show that this system efficiently demethylates both guaiacol and an unexpectedly wide variety of lignin-relevant monomers. Structural, biochemical, and computational studies of this novel two-component system elucidate the mechanism of its broad substrate specificity, presenting it as a new tool for a critical step in biological lignin conversion.

Publication types

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

MeSH terms

  • Actinobacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Lignin / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases, O-Demethylating / chemistry
  • Oxidoreductases, O-Demethylating / metabolism*
  • Protein Multimerization
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Lignin
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases, O-Demethylating