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

Area of Science:

• Biochemistry
• Biotechnology
• Microbial Engineering

Background:

• S-Adenosyl-L-methionine (SAMe) is a vital bioactive sulfur-containing amino acid.
• Efficient large-scale preparation of SAMe is of significant industrial importance.
• SAMe is synthesized from L-methionine and adenosine triphosphate, catalyzed by methionine adenosyltransferase.

Purpose of the Study:

• To review and analyze strategies for enhancing S-Adenosyl-L-methionine biosynthesis in industrial microbial strains.
• To provide a contemporary account of developments in SAMe production.
• To identify potential methods for further improving SAMe biosynthesis efficiency.

Main Methods:

• Genetic manipulation, including overexpression of methionine adenosyltransferase in Pichia pastoris, Saccharomyces cerevisiae, and Escherichia coli.
• Molecular evolution and promoter engineering for fine-tuning enzyme expression.
• Gene modification strategies such as knocking in Vitreoscilla hemoglobin and knocking out cystathionine-β-synthase.
• Bioprocess optimization, including feeding strategies for methanol, glycerol, and L-methionine substrates.

Main Results:

• Considerable improvements in S-Adenosyl-L-methionine accumulation have been achieved at both flask and fermenter scales.
• Genetic modifications targeting methionine adenosyltransferase expression and activity have proven effective.
• Bioprocess strategies, including optimized substrate feeding, contribute to enhanced SAMe synthesis and reduced conversion.

Conclusions:

• Various genetic and bioprocess strategies have successfully enhanced S-Adenosyl-L-methionine biosynthesis.
• Further improvements in SAMe production efficiency are achievable through continued research and development.
• Optimized microbial strains and bioprocesses are key to meeting the demand for large-scale SAMe preparation.