Efficient whole-cell biosynthesis of S-adenosyl-L-methionine by the engineered <i>Escherichia coli</i> with high ATP regenerating system

S-adenosyl-L-methionine (SAM) is an important intermediate metabolite and widely used in the treatment of liver disease, arthritis, and depression. In this work, a whole-cell catalysis strategy was employed to enhance SAM production by combining the SAM biosynthetic pathway with an adenosine triphosphate (ATP) regeneration system in <i>Escherichia coli.</i> Specifically, the <i>ado1</i>, <i>ack</i>, and <i>adk</i> genes were previously introduced into the genome of the host strain. We then confirmed the availability of the ATP regeneration system under the condition of adding adenosine monophosphate (AMP) and acetyl phosphate (ACP) as supplements. To improve the SAM production, the <i>sam2</i> gene derived from <i>Saccharomyces cerevisiae</i> was overexpressed using the plasmid pGEX-2TK in the strain and the conditions of biocatalytic process were optimized. Under the optimal biocatalytic conditions, the recombinant strain RS01 (pGEX-2TK-SAM2) achieved a SAM titer of 11.4 g/L after 10 h cultivation. This work not only provides a new platform for the efficient production of SAM but also offers insights into the biosynthesis of other ATP-dependent products.