Biochemical and structural characterization of enzymes in the 4-hydroxybenzoate catabolic pathway of lignin-degrading white-rot fungi

• Published in: Cell reports (Cambridge) 2024-12, Vol.43 (12), p.115002, Article 115002
• Main Authors: Kuatsjah, Eugene, Schwartz, Alexa, Zahn, Michael, Tornesakis, Konstantinos, Kellermyer, Zoe A., Ingraham, Morgan A., Woodworth, Sean P., Ramirez, Kelsey J., Cox, Paul A., Pickford, Andrew R., Salvachúa, Davinia
• Format: Article
• Language: English
• Subjects: Aromatic catabolism; biotechnology; CP: Metabolism; Gelatoporia subvermispora; lignin valorization; oxygenase; Trametes versicolor
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.115002

White-rot fungi (WRF) are the most efficient lignin-degrading organisms in nature. However, their capacity to use lignin-related aromatic compounds, such as 4-hydroxybenzoate, as carbon sources has only been described recently. Previously, the hydroxyquinol pathway was proposed for the bioconversion of these compounds in fungi, but gene- and structure-function relationships of the full enzymatic pathway remain uncharacterized in any single fungal species. Here, we characterize seven enzymes from two WRF, Trametes versicolor and Gelatoporia subvermispora, which constitute a four-enzyme cascade from 4-hydroxybenzoate to β-ketoadipate via the hydroxyquinol pathway. Furthermore, we solve the crystal structure of four of these enzymes and identify mechanistic differences with the closest bacterial and fungal structural homologs. Overall, this research expands our understanding of aromatic catabolism by WRF and establishes an alternative strategy for the conversion of lignin-related compounds to the valuable molecule β-ketoadipate, contributing to the development of biological processes for lignin valorization. [Display omitted] •We characterize enzymes in the 4-hydroxybenzoate catabolic pathway of white-rot fungi•We identify mechanistic differences between bacterial and fungal structural homologs•We expand our understanding of monomeric aromatic compound catabolism by white-rot fungi•We establish an enzymatic strategy to convert lignin-related compounds to β-ketoadipate Kuatsjah et al. biochemically and structurally characterize enzymes in the 4-hydroxybenzoate catabolic pathway of white-rot fungi. Their findings advance the understanding of aromatic catabolism in fungi and reveal pathways and enzymes that convert lignin-derived compounds into valuable biochemicals, such as β-ketoadipate.