Environmental and Economic Benefits from Strain and Bioprocess Improvements for Sustainable Production of 3-Hydroxypropanoic Acid in a Sugarcane Biorefinery

Biobased 3-hydroxypropanoic acid (3-HP) is a highly sought-after platform chemical with growing global demand. Direct microbial conversion of sugars to 3-HP is a promising alternative to fossil fuel-based production, with the potential to reduce greenhouse gas (GHG) emissions. This study examines the impacts of technological advancements in 3-HP yield, titer, and volumetric productivity, focusing on the minimum selling price (MSP) and life cycle GHG emissions for biorefineries producing 3-HP from sugarcane A-molasses. Biorefinery scenarios representing the complete range of alternative and theoretical bioprocess performances, generated using flux balance analysis (FBA), were simulated in Aspen Plus. FBA showed that theoretical yields from cytosolic 3-HP production in Saccharomyces cerevisiae were similar for the malonyl-CoA, β-alanine, and oxaloacetate pathways (0.801–0.824 g_3-HP·g^–1_glucose), whereas the maximum yield from the oxaloacetate pathway in the cytosol of Komagataella pastoris was 16–21% higher. Mitochondrial localization of the malonyl-CoA pathway in S. cerevisiae led to the highest yield (0.853 g_3-HP·g^–1_glucose), while only slight improvements were seen in K. pastoris. 3-HP production by Corynebacterium glutamicum was economically viable, with an MSP 33.8% below the current fossil-based market price. Fully optimized bioprocesses would reduce the MSP by a similar amount and lower GHG emissions by 43.0% compared with the baseline.