Enhanced d-pantothenic acid biosynthesis by plasmid-free Escherichia coli through sodium pyruvate addition combined with glucose and temperature control strategy

AIMS: d-pantothenic acid (d-PA) is an important vitamin widely used in the feed, pharmaceutical, and food industries. This study aims to enhance the d-PA production of a recombinant Escherichia coli without plasmid and inducer induction. METHODS AND RESULTS: The fermentation medium in shake flask was optimized, resulting in a 39.50% increased d-PA titer (3.32 g l-1). Subsequently, the fed-batch fermentation in a 5-l fermenter was specifically investigated. First, a two-stage temperature control strategy led to a d-PA titer of 52.09 g l-1. Additionally, a two-stage glucose feeding was proposed and d-PA titer was increased to 65.29 g l-1. It was also found that an appropriate amount of sodium pyruvate was beneficial to cell growth and d-PA synthesis. Finally, a two-stage glucose feeding combined with sodium pyruvate addition resulted in a substantially improved d-PA production with a titer of 72.90 g l-1. CONCLUSION: The d-PA synthesis was significantly improved through the fermentation process established in this work, i.e. sodium pyruvate addition combined with the temperature and glucose control strategy. The results of this study could provide significant reference for the industrial fermentation production of d-PA.