Introduction: In industry, α-ketoglutaric acid (KGA) is produced by chemical synthesis. A more promising approach is the microbiological synthesis of KGA using the yeast Yarrowia lipolytica. This approach allows for the production of a high-quality product, which is of significant interest to the food and pharmaceutical industries. Ethyl alcohol, glycerol, vegetable oils, and n-alkanes can be employed as the carbon sources for KGA production by Y. lipolytica. Despite the extensive body of literature on the biosynthesis of KGA by Y. lipolytica, there is no information on scale-up experiments. Concurrently, the approbation of the technology for the synthesis of KGA in pilot bioreactors is a prerequisite for the transition to industrial production.

Methods: The yeast strain Y. lipolytica VKM Y-2412 was cultivated in a 1000-liter SGI bioreactor (Setric Genie Industriel, Toulouse, France) with 400 liters of Reeder medium at 30°C.

Results and Discussion: For the first time, it was demonstrated that it is feasible to produce KGA under pilot conditions. Additionally, technological approaches to realisation of the process were developed. The producer demonstrated optimal growth at a pH of 4.5 and a dissolved oxygen (pO₂) level of 25% saturation during the first two days. Following a two-day period, the production of KGA commenced. Throughout the acid production process, the pH and aeration levels were maintained at 3.5 and 50-55%, respectively. Additionally, rapeseed oil was added at a concentration of 20 g/L when the pO₂ value increased by 10% above the stable level. After 140 hours of cultivation, Y. lipolytica VKM Y-2412 produced 42 g/L of KGA, representing 30% of the rapeseed oil consumed.

Conclusions: This research constituted the first attempt to produce KGA in a large-scale bioreactor. Further research could be conducted to optimize the cultivation conditions at the pilot scale in order to increase the product yield.