Poster Presentation The 48th Lorne Conference on Protein Structure and Function 2023

Efficient O-demethylation of lignin monoaromatics using the peroxygenase activity of cytochrome P450 enzymes (#344)

Alix C Harlington 1 , Keith E Shearwin 1 , Stephen G Bell 2 , Fiona Whelan 1
  1. Department of Molecular and Biomedical Science, The University Of Adelaide, Adelaide
  2. Department of Chemistry, The University Of Adelaide, Adelaide

The aromatic polymer lignin is the second most abundant polymer found on Earth. Found naturally in terrestrial plants, lignin is a common waste product of the paper and biofuel industries. The biological valorisation of lignin has the potential to supply useful chemicals and materials traditionally derived from non-renewable feedstocks. However, a roadblock limiting efficient microbial valorisation of lignin is the availability of enzymes that catalyse the rate limiting O-demethylation of lignin derived aromatic compounds (LDACs). We have biochemically and structurally characterised a bacterial Cytochrome P450 from Amycolatopsis thermoflava N1165 (SyoA) that catalyses the O-demethylation of the underutilised LDAC syringol. We demonstrate that SyoA and the guaiacol O-demethylase GcoA are peroxygenases that can use H2O2 to catalyse the O-demethylation of their substrates. The high-resolution structure (1.3 Å) of SyoA reveals structural differences that are critical in distinguishing between guaiacol and syringol based O-demethylases and the mechanisms involving peroxygenase activity. This work expands the toolkit for the enzymatic bioconversion of S-type lignin and allows for a cheap and clean method for the O-demethylation of aromatics compared to nicotinamide cofactor-dependent monooxygenase systems.