A Promiscuous Cytochrome P450 Aromatic O-Demethylase for Lignin Bioconversion

Sam J.B. Mallinson, Melodie M. Machovina, Rodrigo L. Silveira, Marc Garcia-Borràs, Nathan Gallup, Christopher W. Johnson, Mark D. Allen, Munir S. Skaf, Michael F. Crowley, Ellen L. Neidle, Kendall N. Houk, Gregg T. Beckham, Jennifer L. Dubois, John E. McGeehan

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123 Scopus Citations


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.

Original languageAmerican English
Article number2487
Number of pages12
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

NREL Publication Number

  • NREL/JA-5100-71206


  • enzyme characterization
  • enzyme discovery
  • lignin conversion
  • protein family


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