Low Oxygen Availability Increases Itaconate Production by Ustilago maydis

Itaconic acid is a monomer for high performance polymers. While produced in industry with the filamentous fungi Aspergillus terreus, the production with the smut fungus Ustilago maydis was proposed recently. The strict aerobic process suffers from high power input via gassing and stirring. Here, we investigated in detail possible scenarios for the reduction of energy use during cultivation. In contrast to fermentations with other organic acids, in which even small oxygen concentrations in the medium hinders production, low oxygen availability correlated with increased itaconic acid titer and yield. This is somewhat surprising, as not only the sensitivity of itaconic acid producing U. maydis to oxygen deprivation was previously reported, but also the lower degree of reduction compared to glucose is not directly arguing for improved yield. Scale ups from 0.4 to 30 L using different criteria confirmed the positive impact of low availability of oxygen on itaconic acid production, suggesting a shift in metabolic pathways under restricted oxygen conditions. Oxygen limitation, encountered more likely in industrial fermenters, can be effectively used as a process control strategy to enhance itaconic acid production in U. maydis, offering a new approach for improving the efficiency of industrial-scale biotechnological production.