Advances in Bio-Based Production of 1,4-Butanediol

1,4-Butanediol (1,4-BDO) is a bulk chemical widely used in the modern chemical industry as a solvent, a precursor for polymers, and an intermediate in fine-chemical synthesis. However, its current industrial production primarily relies on petrochemical processes, which are sensitive to fluctuations in fossil fuel prices and raise environmental concerns. To address these challenges, bio-based production of 1,4-BDO has emerged as a promising alternative. This review summarizes recent advances in the biological synthesis of 1,4-BDO, focusing on three engineered pathways: (i) the central carbon metabolism pathway that consists of glycolysis and the tricarboxylic acid cycle; (ii) the non-phosphorylative pathway that utilizes lignocellulose-derived sugars; and (iii) the synthetic pathway based on one-carbon compounds. Key progress in pathway optimization and substrate utilization is highlighted. The main bottlenecks of large-scale bio-based 1,4-BDO production including product toxicity, trade-offs between cell growth and synthesis, and the gap between laboratory conditions and industrial production are also discussed. Finally, future research directions are proposed to improve the economic viability and environmental sustainability of 1,4-BDO biomanufacturing.