Influence of titer, rate, yield, and scale on the cost and life-cycle emissions of biomanufacturing.

Building a thriving bioeconomy requires microbial hosts that efficiently convert diverse carbon sources at high titer, rate, and yield (TRY). Yet, the impacts of TRY on biofuel production cost and carbon footprint across different stages of strain optimization remain unclear. This study presents a systematic analysis of the individual and combined impacts of TRY and scale for the production of multiple bio-based products, including medium-chain (C13-C15) methyl ketones, bisabolene, and ethanol, from lignocellulosic biomass hydrolysates. The results show nonlinear behavior in both cost and CO2-equivalent footprints as a function of TRY, revealing thresholds and inflection points that can inform research and set better goals for commercialization. Ultimately, selecting process-based biorefinery size, including the production cost and carbon mitigation credits, and achieving near-theoretical yield with a titer and rate of >130 g/l and >2 g/l/h, respectively, are essential to produce economically viable biofuels with low life-cycle emissions.