Shikimic acid biosynthesis in microorganisms: Current status and future direction

Shikimic acid (SA), a hydroaromatic natural product, is used as a chiral precursor for organic synthesis of oseltamivir (Tamiflu®, an antiviral drug). The process of microbial production of SA has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Corynebacterium glutamicum (141.2 g/L) and Escherichia coli (87 g/L) laid a solid foundation for the microbial fermentation production of SA. However, its industrial application is restricted by limitations such as the lack of fermentation tests for industrial-scale and the requirement of growth-limiting factors, antibiotics, and inducers. Therefore, the development of SA biosensors and dynamic molecular switches, as well as genetic modification strategies and optimization of the fermentation process based on omics technology could improve the performance of SA-producing strains. In this review, recent advances in the development of SA-producing strains, including genetic modification strategies, metabolic pathway construction, and biosensor-assisted evolution, are discussed and critically reviewed. Finally, future challenges and perspectives for further reinforcing the development of robust SA-producing strains are predicted, providing theoretical guidance for the industrial production of SA.