High-level production ofd-pantothenic acid from glucose by fed-batch cultivation ofEscherichia coli

d-Pantothenic acid (D-PA) is an essential vitamin widely used in food, feed, chemical, and pharmaceutical industries. AnEscherichia coliplatform was developed for the high-level production of D-PA from glucose through fed-batch cultivation. Initially, the effects of different glucose feeding strategies D-PA synthesis were studied. It was found that D-PA production in glucose control (5 g/L) fed-batch culture reached 24.3 g/L, which was 4.09 times that in the batch culture. Next, the effect of auxotrophic amino acid (isoleucine)-limited feeding on D-PA production was investigated. The results revealed that isoleucine feeding decreased the accumulation of by-product acetic acid and promoted D-PA production significantly. Furthermore, an isoleucine feeding embedded multistage glucose supply strategy was established, and a maximum titer of 39.1 g/L was achieved. To the best of our knowledge, this levels are the highest reported so far in engineeredE. colifor the D-PA production. The developed fed-batch feeding strategy may be useful for the industrial D-PA production byE. coli.

Automated summary

Different glucose feeding strategies and isoleucine-limited feeding had significant impacts on D-PA production. A multistage glucose supply strategy embedded with isoleucine feeding achieved the highest titer of 39.1g/L, the highest reported so far for engineered E. coli production of D-PA.