Tuning molecular weight of poly-γ-glutamic acid: advanced biosynthetic engineering approaches and diversified applications

Poly-γ-glutamic acid (γ-PGA) is a natural biopolymer with broad application potential. Molecular weight (MW) is a key physicochemical parameter governing its structural properties, functional performance, and application scope. Recently, sustainable biosynthesis of γ-PGA with controllable MW has gained attention because of its environmental sustainability and process flexibility. With advances in molecular editing and synthetic regulation, MW-control strategies have shifted from random mutagenesis-based strain improvement to precise gene-engineering regulation. This review surveys natural microbial resources producing γ-PGA with diverse MWs and engineering strategies enabling de novo γ-PGA biosynthesis in multiple microbial chassis. To address limited production efficiency, we summarize metabolic engineering approaches for improving γ-PGA yield and MW tunability, including precursor supply optimization, carbon-flux redistribution, transcriptional regulation, use of non-food renewable substrates, and mitigation of metabolic burden from multi-layered engineering. To promote customized production of low-MW γ-PGA, we highlight hydrolase-centered strategies, emphasizing hydrolase screening, optimization of expression elements, and coordinated regulation of γ-PGA stereochemical configuration. Finally, we review applications of γ-PGA with different MWs in food, biopharmaceutical, and agricultural sectors, critically examine links between molecular characteristics and application requirements, and discuss future functional diversification and industrial-scale development.