Catabolism of lignin-related methoxylated compounds in white-rot fungi utilizes a non-canonical extradiol dioxygenase

Lignin is a highly methoxylated, heterogeneous biopolymer derived from plants. However, the pathways WRF use to metabolize methoxylated aromatic compounds as carbon sources remain unidentified.

Here, we employ a systems biology approach to elucidate the intracellular catabolism of vanillate – a monomethoxylated aromatic compound – in two white-rot fungi (WRF), Gelatoporia subvermispora and Trametes versicolor. We identified and biochemically validated a four-enzyme pathway that converts vanillate into β-ketoadipate – a metabolite that enters central carbon metabolism. This pathway deviates from typical bacterial pathways, where vanillate is initially demethylated and ring-cleaved by intradiol dioxygenases; instead, oxidative decarboxylation occurs prior to ring cleavage by extradiol dioxygenases.