Genetic and metabolic engineering for poly-γ-glutamic acid production: current progress, challenges, and prospects

Accompanied with the developments of gene editing and synthetic biology toolkits, various metabolic engineering strategies have been established for strain improvement to enhance the target metabolite production. Poly-gamma-glutamic acid (gamma-PGA) is a natural biopolymer that mainly produced by Bacillus, and low-level yield hinders its application. To address this problem, numerous approaches have been conducted to increase gamma-PGA yield. In this review, we focus on the genetic and metabolic engineering of microorganism for gamma-PGA production, including strengthening raw materials utilization and precursor supply, enhancing gamma-PGA synthetase gene cluster, transcription regulation engineering, cofactor regeneration, energy engineering and blocking the synthetic pathways of by-products. Meanwhile, to attain the gamma-PGA with different configurations (D/L) and molecular weights, the expression of gamma-PGA synthetase, glutamate racemase and gamma-PGA hydrolase were respectively manipulated. In addition, except for Bacillus, metabolic engineering of other hosts for high-level production of gamma-PGA was also reviewed in this article. Finally, the prospect of metabolic engineering of gamma-PGA production strain was discussed regarding the recent progress, challenge, and trends in this field.

Automated summary

This review focuses on the genetic and metabolic engineering of microorganisms for gamma-PGA production, including strategies to enhance raw materials utilization, precursor supply, gamma-PGA synthetase gene cluster, transcription regulation, cofactor regeneration, energy engineering, and blocking synthetic pathways of by-products. The expression of gamma-PGA synthetase, glutamate racemase, and gamma-PGA hydrolase were manipulated to obtain gamma-PGA with different configurations and molecular weights. The review also discusses the metabolic engineering of other hosts for high-level production of gamma-PGA.