Applications of synthetic biology in developing polysaccharide conjugate vaccines
The precise design and synthesis of carbohydrates with important biological functions and more complex structures is a frontier in synthetic biology.Recently,a novel strategy named Protein Glycan Coupling Technology(PGCT)based on bacterial oligosaccharyltransferases has been developed and widely used in the biosynthesis of bacterial glycoconjugate vaccines,which are one of achievements in modern medicine due to their effectiveness in fighting against infectious diseases.Herein,progress in developing key components for manufacturing glycoconjugate vaccines,such as oligosaccharyltransferases(PglL,PglS,PglB,and TfmP),carrier proteins(CRM197,diphtheria toxoid,recombinant Pseudomonas aeruginosa exotoxin A,and nanoparticles),polysaccharide biosynthesis gene circuits,and glyco-engineered strains is reviewed.Meanwhile,producing glycoconjugate vaccines through fermentation presents advantages in good product quality control for safety and efficacy,low production cost,and environmental-friendly manufacturing.PGCT has potentials to overcome some limitations of chemical conjugation production processes,such as complex purification and high cost,for competitiveness with existing chemical conjugates.As an emerging technology,more technological innovations are needed for PGCT.In the future,the directed evolution of oligosaccharyltransferases,the application of protein nanoparticle carriers,the combination rearrangement of glycosyltransferases,and the optimization of engineered bacterial strains with better metabolic pathways are expected to further promote the biosynthesis of conjugate vaccines.The next few years will be an important and exciting time for PGCT,as recent technological advances are being applied to the development of novel glycoconjugates,and ongoing large-scale clinic trials on the efficacy of glycoconjugate vaccines will also demonstrate the feasibility of this technology,making the future of PGCT vaccinology promising.