Metabolic Engineering for S-Adenosylmethionine Production

S-Adenosylmethionine (SAM) is a pivotal methyl donor and cofactor involved in myriad cellular processes, including transmethylation, transsulphuration and polyamine synthesis. Its high commercial value as a pharmaceutical and nutraceutical agent has spurred efforts to develop sustainable production platforms. Microbial fermentation—particularly using Saccharomyces cerevisiae, Bacillus species, Pichia pastoris and engineered Escherichia coli—remains the method of choice, yet native pathways often suffer from limited precursor availability, cofactor imbalance and feedback inhibition. Metabolic engineering strategies seek to overcome these challenges by rewiring central carbon metabolism to channel ATP and methionine toward SAM biosynthesis, by introducing heterologous or feedback‐insensitive methionine adenosyltransferases, and by employing dynamic control systems to balance growth with product formation. Advances in genome editing, synthetic regulatory circuits and enzyme scaffolding have enabled precise modulation of gene expression and enzyme localisation, while bioprocess optimisation—such as fed-batch feeding of L-methionine and tailored oxygen regimes—has driven titers into the multi-gram per litre range. Such integrated approaches not only enhance SAM yield and productivity but also lay the groundwork for scalable, cost-effective manufacturing of SAM and related methylated compounds with global health and industrial relevance.

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Metabolic Engineering for S-Adenosylmethionine Production publication trend

The graph below shows the total number of articles in metabolic engineering for s-adenosylmethionine production across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolic flux: The rate at which substrates and intermediates flow through a metabolic network.

CRISPR/Cas9 system: A genome-editing technology that enables targeted DNA modifications for strain development.

Methionine adenosyltransferase (MAT): The key enzyme catalysing the condensation of methionine and ATP to form SAM.

Glycolysis: The cytosolic pathway converting glucose into pyruvate with concomitant ATP generation.

Tricarboxylic acid (TCA) cycle: A mitochondrial pathway oxidising acetyl-CoA to CO₂ and generating reducing equivalents and ATP.

Feedback inhibition: A regulatory mechanism where an end product binds to an enzyme and decreases its activity.

References

1. System metabolic engineering modification of Saccharomyces cerevisiae to increase SAM production. Bioresources and Bioprocessing (2025).
2. Increasing glycolysis by deletion of kcs1 and arg82 improved S-adenosyl-l-methionine production in Saccharomyces cerevisiae. AMB Express (2021).
3. The multiple effects of REG1 deletion and SNF1 overexpression improved the production of S-adenosyl-l-methionine in Saccharomyces cerevisiae. Microbial Cell Factories (2022).