Recent advances in microbial production of S-adenosyl-L-methionine and its high-value derivatives

S-Adenosyl-L-methionine (SAM or AdoMet) is a central metabolic hub linking methylation, transsulfuration, and polyamine metabolism. It also serves as the universal methyl donor or aminopropyl donor in the biosynthesis of diverse high-value compounds. This pivotal role is particularly evident in the production of representative SAM-dependent products, including β-methyl-α-amino acids and polyamines, which have broad applications in life science. Despite growing interest in sustainable biomanufacturing, industrial production of SAM and its derivatives still relies heavily on chemical synthesis. This dependence raises concerns about environmental burden and long-term sustainability. Recent advances in systems metabolic engineering and synthetic biology have accelerated the development of microbial platforms for SAM and SAM-derived products biosynthesis. This review summarizes major engineering strategies for improving SAM biosynthesis, utilization, and recycling in microbial systems. Particular emphasis is placed on the role of SAM in the biosynthesis of representative derivatives, including ferulic acid, ergothioneine, creatine, spermidine, and β-methyl-phenylalanine. The application of SAM-related systems metabolic engineering strategies to enhance the production of these compounds is also discussed. Finally, current challenges and future prospects for the efficient and sustainable production of SAM and SAM-dependent high-value compounds are outlined.