Christian Fink, Franziska Steger, Sebastian Schmidt, Elisa Hilts, François Unger, Aquilla Ruddyard, Maximilian Klein, Bart-Jan Akerboom, Thomas Stehrer-Polašek, Stefan Drießler, Shubham Gurav, Ross T Fennessy, Justin Smith, Günther Bochmann, Simon K-M R Rittmann
Beyond their nutritional value, amino acids 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. In this research article, we report an archaeal cell factory for leucine production from CO2 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 CO2 at the 150-L pilot-plant scale with a mean volumetric leucine productivity of 65 mg L-1 h-1. A thorough techno-economic analysis indicates that the rollout of leucine production from CO2 is nearly economically feasible on a global scale.