Pilot-scale production of leucine from CO ₂

On a cellular level, proteinogenic amino acids (AAs) are the building blocks of proteins. On a global scale, AAs serve as important nutrients for humans and animals. Beyond their nutritional value, AAs are of relevance in medicine, and, due to their chemical properties, they are indispensable for applications in many different realms, such as pharmaceutics, cosmetics, animal feed, food, and the beverage industry. Here, we report the first archaeal cell factory for leucine production from CO ₂ that has been generated by rational design, random mutagenesis and pathway engineering. The cell factory has been bioprocess-technologically examined and successfully scaled-up with regard to productivity, product quality, and operational stability. In a 2-day fed-batch campaign, we produced 181 g of leucine from CO ₂ at 150 L pilot-plant scale at a mean volumetric leucine productivity of 65 mg L ^-1 h ^-1 . A thorough techno-economic analysis indicates that the roll-out of leucine production from CO ₂ is nearly economically feasible on a global scale.