Genetic modification and bioprocess optimization for S-Adenosyl-L-methionine biosynthesis.

S-Adenosyl-L-methionine is an important bioactive sulfur-containing amino acid. Large scale preparation of the amino acid is of great significance. S-Adenosyl-L-methionine can be synthesized from L-methionine and adenosine triphosphate in a reaction catalyzed by methionine adenosyltransferase. In order to enhance S-adenosyl-L-methionine biosynthesis by industrial microbial strains, various strategies have been employed to optimize the process. Genetic manipulation has largely focused on enhancement of expression and activity of methionine adenosyltransferase. This has included its overexpression in Pichia pastoris, Saccharomyces cerevisiae and Escherichia coli, molecular evolution, and fine-tuning of expression by promoter engineering. Furthermore, knocking in of Vitreoscilla hemoglobin and knocking out of cystathionine-β-synthase have also been effective strategies. Besides genetic modification, novel bioprocess strategies have also been conducted to improve S-adenosyl-L-methionine synthesis and inhibit its conversion. This has involved the optimization of feeding modes of methanol, glycerol and L-methionine substrates. Taken together considerable improvements have been achieved in S-adenosyl-L-methionine accumulation at both flask and fermenter scales. This review provides a contemporary account of these developments and identifies potential methods for further improvements in the efficiency of S-adenosyl-L-methionine biosynthesis.