d-Pantothenic acid (D-PA) is an essential vitamin widely used in food, feed, chemical, and pharmaceutical industries. An Escherichia coli platform 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 engineered E. coli for the D-PA production. The developed fed-batch feeding strategy may be useful for the industrial D-PA production by E. coli.

中文翻译：

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大肠杆菌补料分批培养葡萄糖高水平生产d-泛酸

d-泛酸 (D-PA) 是一种必需维生素，广泛用于食品、饲料、化工和制药行业。大肠杆菌_平台是为通过补料分批培养从葡萄糖中高水平生产 D-PA 而开发的。最初，研究了不同葡萄糖补料策略对 D-PA 合成的影响。发现葡萄糖对照（5 g/L）分批补料培养中的D-PA产量达到24.3 g/L，是分批培养的4.09倍。接下来，研究了营养缺陷型氨基酸（异亮氨酸）限制喂养对 D-PA 生产的影响。结果表明，异亮氨酸补料减少了副产物乙酸的积累，并显着促进了 D-PA 的产生。此外，建立了异亮氨酸补料嵌入式多阶段葡萄糖供应策略，最高滴度达到 39.1 g/L。据我们所知，这一水平是迄今为止在工程大肠杆菌中报道的最高水平用于 D-PA 生产。开发的分批补料策略可能对大肠杆菌的工业 D-PA 生产有用。