Improved methyl supply for 5-methyltetrahydrofolate production in E. coli through a novel C1 transfer pathway.

ABSTRACT:

Background

L-5-Methyltetrahydrofolate (5-MTHF) is the sole biologically active form of folate present in human blood and serves as an essential nutritional supplement. While microbial biosynthesis of 5-MTHF offers a sustainable alternative to chemical synthesis, its low yield limits industrial potential.

Results

In this study, strategies for improving the methyl supply combined with engineering the tetrahydrofolate (THF) synthetic pathway were employed in E. coli to increase 5-MTHF production. First, a new exogenous C1 pathway was introduced to improve the intracellular methyl supply through acetyl-CoA breakdown. High expression of key rate-limiting genes folE, folP and purU enhanced metabolic flux of THF pathway, resulting in a 5-MTHF titer of 1.075 mg/L during shake-flask

SUBMITTER: Liu W 

PROVIDER: S-EPMC11998260 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature