Improving Microbial Cell Factory Performance by Engineering SAM Availability.

Area of Science:

• Biotechnology
• Metabolic Engineering
• Natural Product Synthesis

Background:

• Methylated natural products are diverse and crucial, with S-Adenosyl-l-methionine (SAM) as the key methyl donor.
• Microbial cell factories (MCFs) are increasingly used for producing SAM-dependent natural products (SdNPs).
• Limited SAM availability and inefficient methyl group supply impede SdNP production in MCFs.

Purpose of the Study:

• To review current knowledge on SAM biosynthesis and regulation in the context of MCF development.
• To identify and evaluate sustainable methyl sources for improving SAM availability.
• To discuss metabolic engineering strategies and genetic circuit design for enhancing SdNP production.

Main Methods:

• Review of literature on SAM biosynthesis pathways and regulatory mechanisms.
• Comparative analysis of different methyl group sources, including one-carbon compounds.
• Examination of metabolic engineering approaches and dynamic regulation strategies for SAM pools.

Main Results:

• SAM biosynthesis is tightly regulated and linked to cellular energy pools (ATP, NAD(P)H).
• Alternative methyl sources, particularly cheap one-carbon compounds, show promise for sustainable production.
• Metabolic engineering and dynamic regulation offer viable strategies to boost intracellular SAM levels.

Conclusions:

• Optimizing methyl source supply and SAM biosynthesis regulation is critical for efficient SdNP production in MCFs.
• Engineering SAM-responsive genetic circuits holds potential for advanced control in MCFs.
• Sustainable production of valuable SdNPs can be achieved through integrated metabolic engineering approaches.