Module engineering coupled with omics strategies for enhancing D-pantothenate production in Escherichia coli.

[Display omitted] • Reinforcement of the precursor supply module enhanced the D-pantothenate production. • Enhancing the supply of one carbon unit module increased the yield of D-pantothenate. • Reinforcement of cofactor and energy provision enhanced D-pantothenate biosynthesis. • Omics analysis characterized metabolic variation and offered targets of modification. • 45.35 g/L D-pantothenate with a yield of 0.31 g/g glucose was produced. Biosynthesis of D-pantothenate has been widely studied as D-pantothenate is one kind of important vitamins used in food and pharmaceuticals. However, the engineered strain for D-pantothenate production was focused solely on the main biosynthetic pathway, while other important factors such as one carbon unit were ignored. Here the systematic modular engineering on different factors coupled with omics analysis were studied in Escherichia coli for efficient D-pantothenate production. Through reinforcing the precursor pool, refactoring the one carbon unit generation pathway, optimization of reducing power and energy supply, the D-pantothenate titer reached 34.12 g/L with the yield at 0.28 g/g glucose under fed-batch fermentation in 5-L bioreactor. With a further comparative transcriptome and metabolomics studies, the addition of citrate was implemented and 45.35 g/L D-pantothenate was accumulated with a yield of 0.31 g/g glucose. The systematic modular engineering coupled with omics studies provide useful strategies for the industrial production of D-pantothenate. [ABSTRACT FROM AUTHOR]