Itaconic acid production from acetate by Ustilago maydis: A step towards land-free biotechnology

Itaconic acid is a versatile bio-based platform chemical produced from sugar-based feedstocks, linking its production to arable land use. As global food demand rises, alternative carbon sources that decouple industrial biotechnology from agriculture are required. The C2 compound acetate can be derived from lignocellulosic biomass and industrial side streams. Emerging routes enable the direct synthesis of acetate from C1 carbon sources such as CO2, CO, and methane. Here, we show that the smut fungus Ustilago maydis can efficiently produce itaconic acid using acetate as the sole carbon source. To overcome weak-acid toxicity and pH-related stress, a combined pH-stat and DO-triggered feeding strategy was applied in a 1 L-scale fed-batch bioreactor, enabling an itaconate titer of 97 g L-1 and an overall yield of 0.41 g g-1. Key performance indicators were comparable to those of a glucose-based reference process. Despite substantially lower biomass formation on acetate, biomass-specific production rates were markedly higher than on glucose, indicating highly efficient channeling of carbon toward product formation. Overall, our results establish acetate as a competitive and sustainable feedstock for fungal itaconic acid production and position acetate-based processes as a viable route toward land-free biotechnology.