α-Ketoglutaric acid as a promising platform chemical for sustainable bio-based industries

The chemical industry is gradually shifting from fossil-derived resources to more sustainable bio-based processes. Natural bio-molecules such as succinic, lactic, and itaconic acid are promising platform chemicals for this green chemistry transition because they can be produced from biomass and converted into various products that are currently produced through fossil-based processes, or they can replace these fossil-based products. One specific bio-molecule, α-ketoglutaric acid (α-KGA), is particularly interesting because it can be directly applied in certain nutrition and healthcare applications, and also serves as a precursor for other commodity and fine chemicals. This review examines the unique chemical properties and application potential of α-KGA and summarises the current state-of-the-art in chemical synthesis and microbial production of α-KGA. Specifically, we discuss how recent advances in precision fermentation, microbial metabolic engineering, and downstream purification are opening new avenues towards sustainable α-KGA production from renewable feedstocks such as sugars, glycerol, fatty acids, alkanes, and alcohols, with titres reaching up to 195 g L^-1 and productivity up to 1.75 g L^-1 h^-1. Finally, we critically assess the future potential and remaining challenges to implement a cost-competitive industrial bio-based α-KGA chemistry.