D-pantothenic acid (D-PA) is an essential vitamin that has been widely used in medicine, food, and animal feed. Microbial production of D-PA from natural renewable resources is attractive and challenging. In this study, both strain improvements and fermentation process strategies were applied to achieve high-level D-PA production in Escherichia coli. First, a D-PA-producing strain was developed through deletion of the aceF and mdh genes combined with the overexpression of the gene ppnk. The obtained engineered E. coli DPA02/pT-ppnk accumulated 6.89 ± 0.11 g/L of D-PA in shake flask fermentation, which was 79.9 % higher than the control strain. Moreover, the cultivation process contributed greatly to D-PA production with respect to titer and productivity by betaine supplementation and dissolved oxygen (DO)-feedback feeding framework. Under optimal conditions, 68.3 g/L of D-PA, the specific productivity of 0.794 g/L h and the yield of 0.36 g/g glucose in 5 L fermenter were achieved. Overall, this research successfully exploited advanced strategies to lay the foundation for bio-based D-PA production in industrial applications.

D-泛酸 (D-PA) 是一种必需的维生素，已广泛用于医药、食品和动物饲料。从天然可再生资源中微生物生产 D-PA 既有吸引力又具有挑战性。在这项研究中，菌株改进和发酵工艺策略被应用于在大肠杆菌中实现高水平的 D-PA 生产。首先，通过删除aceF和mdh基因并结合基因ppnk的过表达，开发了产生 D-PA 的菌株。得到的工程大肠杆菌DPA02/pT- ppnk在摇瓶发酵中积累了 6.89 ± 0.11 g/L 的 D-PA，比对照菌株高 79.9%。此外，培养过程通过补充甜菜碱和溶解氧 (DO)-反馈进料框架对 D-PA 生产的效价和生产力做出了巨大贡献。在最佳条件下，5 L发酵罐中D-PA的产量为68.3 g/L，比生产率为0.794 g/L h，葡萄糖产量为0.36 g/g。总的来说，这项研究成功地利用了先进的策略，为工业应用中的生物基 D-PA 生产奠定了基础。