On a cellular level, proteinogenic amino acids (AAs) are the building blocks of 16 proteins. On a global scale, AAs serve as important nutrients for humans and 17 animals. Beyond their nutritional value, AAs are of relevance in medicine, and, due to 18 their chemical properties, they are indispensable for applications in many different 19 realms, such as pharmaceutics, cosmetics, animal feed, food, and the beverage 20 industry. Here, we report the first archaeal cell factory for leucine production from 21 CO2 that has been generated by rational design, random mutagenesis and pathway 22 engineering. The cell factory has been bioprocess-technologically examined and 23 successfully scaled-up with regard to productivity, product quality, and operational 24 stability. In a 2-day fed-batch campaign, we produced 181 g of leucine from CO2 at 150 L pilot-plant scale at a mean volumetric leucine productivity of 65 mg L-1 h-1 25 . A 26 thorough techno-economic analysis indicates that the roll-out of leucine production 27 from CO2 is nearly economically feasible on a global scale.