Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application

Since its discovery as a pivotal enzyme in innate immunity, cyclic GMP-AMP synthase (cGAS) has been extensively studied for its immunological significance and catalytic mechanism. However, its potential as a biocatalyst for the efficient synthesis of the second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP) remains underexplored. This review provides a comprehensive biotechnological perspective on cGAS, highlighting its enzymatic and structural features, substrate promiscuity, homologs, and engineered variants. We examined the expression systems reported in previous studies and assessed their suitability for scalable cGAS production. Furthermore, we explored reaction engineering strategies for 2'3'-cGAMP synthesis by comparing published production and purification methods. This review aims to bridge the gap between fundamental enzymology and applied bioprocessing by positioning cGAS as a promising biocatalyst for the pharmaceutical industry, with potential applications in immunotherapy, vaccine adjuvants, and beyond.