Abstract
BACKGROUND: 1,3-Propanediol (PDO) is a high value-added product with significant potential for application and development in various industries including textiles, cosmetics, food, and chemicals. Microbial fermentation for 1,3-PDO production has advantage over chemical synthesis in response to environmental and energy challenges. In view of the complexity and benefits of biometabolic synthesis, there is a necessity to enhance the yield of 1,3-PDO to glycerol by means of co-substrates, whilst concomitantly reducing the cost of production. RESULTS: In this study, the efficiency and cost-effectiveness of 1,3-PDO synthesis by Clostridium butyricum DL07 were improved through elucidating the regulatory mechanism of glucose-glycerol cometabolism and optimizing the ratio of co-substrates. Among the screened co-substrates, glucose emerged as the optimal choice for enhancing the yield and concentration of 1,3-PDO synthesized from glycerol. If the molar ratio of glucose to glycerol was 0.51 mol/mol, the 1,3-PDO yield reached 0.90 mol/mol in the co-substrate fermentation. Real-time quantitative PCR revealed that the dha operon expression was affected by glucose on inhibition of GDH (dhaD) and phasically upregulation of PDOR activity (dhaT). Stoichiometric analysis combined with further optimization of the different feeding strategies increased the 1,3-PDO yield to the highest level of fed-batch fermentation (0.86 mol/mol) reported to date for natural strains. The material cost analysis demonstrated that the co-substrate strategy reduced raw material cost by 13–20%. CONCLUSIONS: This study presents an investigation into the synthesis of 1,3-PDO through cometabolism in C. butyricum DL07. The research elucidates the synergistic impact of co-substrate ratios and temporal regulation on the synthesis of 1,3-PDO. Moreover, it offers a theoretical basis and a practical approach for achieving cost-effective and efficient industrial production. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-026-02971-6.