Toward a CO2-neutral biotechnology: itaconate production using CO2 derived co-substrates

Climate change represents a severe global issue also driven by the consumption of fossil fuels, which ultimately release greenhouse gases into the atmosphere. Simultaneously, the rising demand for food, energy, and chemicals requires a shift from fossil to sustainable raw materials. Utilizing renewable carbon sources (i.e., biomass, CO2, organic waste) ensures a fossil-free future. Over recent years, itaconate has gained increasing interest as a prospective bio-based platform chemical. To replace nowadays petroleum-derived substances like methacrylic acid in industrial applications, enhancing the economic viability of the current biotechnological production processes using the fungus Aspergillus terreus is essential.Ustilaginaceae, a family of smut fungi, display a broad product spectrum featuring organic acids (e.g., itaconate, malate, succinate). These molecules are considered value-added chemicals with potential applications in the pharmaceutical, food, and chemical industry. Importantly, in combination with feeding alternative C-sources as (co-)substrates (e.g., acetate, formate, lignocellulose), these microorganisms offer excellent potential for reducing CO2 emissions and land use. This thesis focused on bioprocess optimization and metabolic engineering strategies to establish a sustainable, industrially relevant Ustilaginaceae itaconate production host competitive to A. terreus. Concerning the bioprocess optimization aspect, acetate and formate were inverstigated as co-substrates. Investigating the biodiversity using in total 72 Ustilaginaceae, Ustilago maydis MB215 and Ustilago cynodontis NBRC 9758 were identified as potential production hosts using these co-substrates in combination with glucose. Formate was supplied from chemical CO2 hydrogenation reactions using a biphasic Ru-catalyst without any purification, highlighting the many possibilities of combining chemo- and biocatalysis for carbon capture and utilization. Long-term itaconate production during