Work

Construction and application of an efficient methylation platform in Escherichia coli based on SAM regeneration

Year: 2025

Type: article

Abstract: Methylation reactions are involved in the synthesis of various natural molecules, but the limited supply of intracellular S-adenosylmethionine (SAM) poses a challenge for the large-scale microbial production of methylated compounds. In this study, we conducted a comprehensive analysis and optimization of the SAM cycle regeneration pathway, enhancing the methylation efficiency in three key steps of the pathway (SAM carbon skeleton cycle, 5-methyltetrahydrofolate cycle, and adenine-ATP cycle), and constructed an efficient endogenous methylation platform in E. coli . This platform significantly increased the intracellular level of the cofactor SAM and improved methylation efficiency. Using this platform, the production of methylated products, including ferulic acid , vanillyl alcohol, and melatonin , increased by 4.2-fold, 1.28-fold, and 44.6 %, respectively. Notably, the ferulic acid titer reached 7.24 g/L, marking the highest level reported to date. These findings demonstrate the broad applicability of this methylation platform, providing a generalizable and effective approach for the biosynthesis of a wide range of SAM-dependent products.

Source: Chemical Engineering Journal

DOI: 10.1016/j.cej.2025.162642