The global transition towards a sustainable bioeconomy requires efficient microbial platform organisms capable of converting renewable carbon sources into valuable chemicals. This dissertation is dedicated to the development of a sustainable bioprocess for the microbial production of α-ketoglutarate (AKG), an important platform chemical with applications including functional polymers. The first part focuses on comprehensive bioprocess development with Corynebacterium glutamicum using molasses, a sugar-rich industrial side stream of 1st generation. Through the combination of rational strain engineering with automated high-throughput phenotyping and scale-up in the upstream process, an efficient bioprocess was established (YP/S = 0. 59 Cmol Cmol⁻¹). The development of a downstream concept based on liquid-liquid extraction followed by crystallization enabled the recovery of highly pure AKG. The second part focuses on the utilization of lignocellulosic side streams for AKG production. The technical challenges of process development, in particular inhibitory by-products in the hydrolysate and the efficient co-utilization of glucose and xylose were addressed. In addition, sustainability and economic aspects are discussed, with particular emphasis on the potentials and challenges of valorizing agro-industrial residues. In the third part ethanol as an alternative carbon and energy source for microbial production with C. glutamicum is investigated. To overcome the metabolic limitations of the wild-type strain in ethanol utilization, adaptive laboratory evolution (ALE) experiments were conducted. The core technology for miniaturized and automated ALE was fundamentally expanded, enabling the implementation of long-term ALE. The ethanol-evolved strain WTEtOH-evo exhibited significantly improved growth and ethanol utilization. Proteomic and genomic analyses identified a single nucleotide mutation affecting the regulation of acetaldehyde dehydrogenase expression. Initial experiments confirmed the feasibility of AKG production from ethanol (YP/S = 0. 11 Cmol Cmol⁻¹). Taken together, this thesis demonstrates the establishment of an efficient bioprocess for AKG production and its extension to diverse renewable carbon sources, underlining the potential of C. glutamicum as a versatile platform organism for sustainable bioproduction.
Lars Niklas Halle (Thu,) studied this question.