Poster Presentation The 47th Lorne Conference on Protein Structure and Function 2022

The hunt for the elusive S-lignin O-demethylase (#123)

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

Lignin is an abundant and complex aromatic polymer found in plants comprised predominately of p-coumaryl (H type), coniferyl (G type), and sinapyl (S type) alcohol subunits. The biological valorisation of lignin offers a green alternative to the production of commercially useful products which have been traditionally synthesised from unsustainable sources. Developments in lignin depolymerisation have provided the opportunity for lignin-derived aromatic compounds (LDACs) to be directed towards chemically useful products. However, a roadblock towards efficient lignin valorisation is the availability of enzymes which catalyse the rate limiting O-demethylation of LDACs. Several cytochrome P450 O-demethylases have been characterised that act on G and H type LDACs [1]. However, no native S type O-demethylase has previously been identified. Thus, the bioconversion of LDACs derived from S lignin – which is abundant in hardwood and grasses - is limited. In this work, we have characterised a novel bacterial cytochrome P450 enzyme from Amycolatopsis thermoflava capable of catalysing the O-demethylation of syringol – a major LDAC of S type lignin. Homology modelling and in silico docking were used to determine the binding specificity of the cytochrome P450 and in vitro UV/vis spectroscopy and hydrogen peroxide turnovers were used to verify binding and catalysis. The discovery and characterisation of S type lignin O-demethylases will enable the development of engineered microbes for the efficient valorisation of heterogeneous lignin to commercially useful products.

  1. Wolf, ME, Hinchen, DJ, DuBois, JL, McGeehan, JE & Eltis, LD 2021, 'Cytochromes P450 in the biocatalytic valorization of lignin', Current opinion in biotechnology, vol. 73, pp. 43-50.