Nonengineered Fungus Provides a Shortcut from Cellulose to Bulk Erythro-isocitric Acid

The biotechnological valorization of renewable lignocellulose into chemical building blocks, such as organic acids, has been defined as a cornerstone for the transition to a sustainable bioeconomy. Yet, large-scale commercialization is hampered by a complex multistage process. Therefore, the integration of cellulase production, cellulose hydrolysis, and product fermentation into a single step is considered a breakthrough technology offering a real economic advantage. Here, we demonstrate that the natural fungus Talaromyces verruculosus can directly convert cellulose into enantiopure erythro-isocitric acid, a chiral isomer of citric acid with high potential as a chemical building block. With a peak productivity of 0.7 g/(L h), the process performance is comparable to established glucose-based fermentations. A titer of 38.4 g/L was reached with a yield of 0.64 g/g consumed cellulose. The analysis of conflicting subprocess requirements reveals why this natural biocatalyst has been overlooked for decades.