Shikimic acid biosynthesis in microorganisms: Current status and future direction

Area of Science:

• Biotechnology
• Metabolic Engineering
• Natural Product Synthesis

Background:

• Shikimic acid (SA) is a vital chiral precursor for oseltamivir (Tamiflu).
• Microbial production of SA has advanced significantly, with high yields reported in recombinant Corynebacterium glutamicum and Escherichia coli.
• Industrial application is hindered by scale-up challenges and reliance on specific growth factors.

Purpose of the Study:

• To review recent advancements in developing robust SA-producing microbial strains.
• To critically analyze genetic modification strategies, metabolic pathway construction, and biosensor-assisted evolution.
• To identify future challenges and perspectives for industrial SA production.

Main Methods:

• Review of literature on genetic engineering and metabolic pathway optimization for SA production.
• Analysis of biosensor development and omics-based strategies for strain improvement.
• Evaluation of fermentation process optimization techniques.

Main Results:

• High SA titers (141.2 g/L in C. glutamicum, 87 g/L in E. coli) achieved through strain engineering.
• Identification of limitations including scale-up, growth factors, antibiotics, and inducers.
• Highlighting the potential of biosensors and omics technologies for enhancing SA production.

Conclusions:

• Significant progress in microbial SA production necessitates further research into industrial-scale fermentation.
• Development of SA biosensors, molecular switches, and omics-guided strategies are crucial for strain improvement.
• Future efforts should focus on overcoming current limitations to enable efficient industrial SA manufacturing.