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

Abstract 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 C 2 compound acetate can be derived from lignocellulosic biomass and industrial side streams. Emerging routes enable the direct synthesis of acetate from C 1 carbon sources such as CO 2 , 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.