Uncovering lignin metabolism in Myceliophthora thermophila toward integrated lignocellulose valorization.

Abstract

Lignin accounts for up to one-third of plant biomass, making it the second most abundant biopolymer on Earth. The thermophilic ascomycete Myceliophthora thermophila is a well-established platform to produce chemicals from plant biomass. However, its capacity for lignin metabolism remains largely unexplored. This study demonstrates that M. thermophila can remodel lignin and metabolize a broad spectrum of lignin-derived aromatic monomers. By integrating transcriptomic profiling with targeted gene deletions, we mapped the key metabolic pathways for these aromatic compounds. Specifically, we found that M. thermophila funnels diverse p-hydroxyphenyl (H) and guaiacyl (G) aromatic monomers into the 3,4-dihydroxybenzoic acid (protocatechuic acid, 3,4-DHB) branch of the β-ketoadipate pathway. Disrupting the protocatechuate hydroxylase and 3,4-dioxygenase genes successfully redirected metabolic flux, achieving 42.5‒95.8% molar yields of 3,4-DHB from H- and G-type monomers. Notably, the engineered strains achieved direct 3,4-DHB production from raw corncob. These findings provide new insights into the metabolism of lignin-derived aromatic compounds in M. thermophila and establish a foundation for integrated lignocellulose biorefineries and aromatic bioprocessing.