Improved production of D-pantothenic acid in Escherichia coli by integrated strain engineering and fermentation strategies

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 DPA production in industrial applications.