Thermodynamics-based design of microbial cell factories for anaerobic product formation

• Thermodynamic feasibility is the first requisite for more rational strain design.
• ΔeG-based assessment identifies compounds that could be produced anaerobically.
• The present approach allows a feasibility check with minimum data input.
• Many compounds on the DOE list could be produced anaerobically.

The field of metabolic engineering has delivered new microbial cell factories and processes for the production of different compounds including biofuels, (di)carboxylic acids, alcohols, and amino acids. Most of these processes are aerobic, with few exceptions (e.g., alcoholic fermentation), and attention is focused on assembling a high-flux product pathway with a production limit usually set by the oxygen transfer rate. By contrast, anaerobic product synthesis offers significant benefits compared to aerobic systems: higher yields, less heat generation, reduced biomass production, and lower mechanical energy input, which can significantly reduce production costs. Using simple thermodynamic calculations, we demonstrate that many products can theoretically be produced under anaerobic conditions using several conventional and non-conventional substrates.