Biomanufacturing provides a more sustainable alternative to fossil-based chemical manufacturing. Here we report the development of a microbial fermentation process to cost-effectively produce an industrially important commodity chemical 3-hydroxypropionic acid (3HP) at industrial pilot scale. We first used metabolic engineering to create a non-model yeast, Issatchenkia orientalis SD108 capable of converting glucose and carbon dioxide (CO2) to 3HP with high titer (92 g/L) and yield (0.7 g/g glucose) at low pH (pH 4) in a 0.3 L fermenter via fed-batch fermentation. We then scaled up the fermentation process by 1000x to 300 L using low-cost media (corn steep liquor, CSL), glucose and CO2, achieving a 3HP titer of 62.5 g/L and a yield of 0.73 g/g glucose. Moreover, we developed a simple downstream processing (DSP) strategy to recover 3HP as sodium salt in purity of 83.2% w/w and recovery of 77.31% w/w. Finally, we demonstrated the financial viability of the end-to-end 3HP production process and the potential to achieve a more environmentally beneficial production (i.e., with substantially reduced carbon intensity and fossil energy consumption compared to fossil-based production). Our work has provided a general framework for developing cost-effective biomanufacturing processes for industrial chemicals.
