Identifying Metabolic Pathway Intermediates That Modulate The Gallate Dioxygenase (Desb) From Sphingobium Sp. Strain Syk-6

Lignin is often considered an underutilized carbon source for the production of biofuels and other value-added compounds. Depolymerized lignin results in a collection of different aromatic compounds that have their own metabolic pathways for conversion into central metabolites. This investigation describes the chemical crosstalk of compounds between different metabolic pathways involved in the catabolism of lignin. Specifically, seven compounds were identified as inhibitors of the dioxygenase DesB. The most potent inhibitor, protocatechuate, moderately impacts both v(max) and K-M of DesB (71 s(-1) and 167 mu M versus 130 s(-1) and 123 mu M, in the presence and absence of protocatechuate, respectively) suggesting a mixed (competitive and non-competitive) inhibition profile. Molecular docking identified a putative allosteric pocket adjacent to the active site, in a position analogous to one identified previously for a related dioxygenase. This work demonstrates that lignin catabolic pathway intermediates can modulate the activity of multiple enzymes within the lignin degradation pathway and need to be considered when engineering organisms to utilize lignin for biomass conversion.