Metabolic engineering of Escherichia coli for enhanced production of D-pantothenic acid.

D-pantothenic acid (D-PA) is an essential vitamin that has been widely used in various industries. However, the low productivity caused by slow D-PA production in fermentation hinders its potential applications. In this study, strategies of engineering the synthetic pathway combined with regulating methyl recycle were employed in E. coli to enhance D-PA production. First, a self-induced promoter-mediated dynamic regulation of D-PA degradation pathway was carried out to improve D-PA accumulation. Then, to drive more carbon flux into D-PA synthesis, the key nodes of the R-pantoate pathway which encoded the essential enzyme were integrated into the genome. Subsequently, the further increase in D-PA production was achieved by promoting the regeneration of methyl donor. The strain L11T produced 86.03 g/L D-PA with a productivity of 0.797 g/L/h, which presented the highest D-PA titer and productivity to date. The strategies could be applied to constructing cell factories for producing other bio-based products.