Advances in metabolic engineering and fermentation for 3-hydroxypropionic acid biosynthesis: a comprehensive review

The grand challenge in biobased Manufacturing Lies in achieving the sustainable, economically competitive conversion of renewable biomass into high-value Chemicals capable of replacing fossil-derived products. Among these, 3-hydroxypropionic acid (3-HP) has emerged as a top-tier target-an exceptionally versatile platform molecule. It finds applications in the synthesis of acrylic acid, 1,3-propanediol, and other derivatives, positioning it as a potential cornerstone for bio-based plastics. This review consolidates the latest breakthroughs in microbial 3-HP production, encompassing advanced strain engineering, pathway rewiring, cofactor optimization, metabolic modeling, and flux balance analysis. We critically examine strategies to overcome inherent metabolic and physiological constraints, including byproduct suppression, redox balancing, and tolerance engineering. Emerging approaches-such as dynamic regulation of metabolic flux, control of cell morphology and density, and integration of co-production pathways-are highlighted for their capacity to boost yields and process robustness. Additionally, we address the fermentation process innovations targeting enhanced productivity, substrate efficiency, minimal nutrient input, and industrially relevant titres. Collectively, these insights Chart a clear path toward the scalable, sustainable biomanufacturer of 3-HP.