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

## TL;DR

This review explores cGAS as a potential biocatalyst for pharmaceutical applications, focusing on its enzymatic properties and scalable production methods.

## Contribution

The paper bridges fundamental enzymology with industrial bioprocessing by evaluating cGAS for large-scale 2′3′-cGAMP synthesis.

## Key findings

- cGAS exhibits substrate promiscuity and structural features suitable for biocatalytic applications.
- Expression systems and reaction engineering strategies for scalable cGAS production are evaluated.
- cGAS is positioned as a promising tool for pharmaceutical manufacturing, including immunotherapy and vaccine adjuvants.

## Abstract

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.

This review examines the structural and enzymatic properties of cyclic GMP‐AMP synthase, including substrate promiscuity, homologs, and engineered variants. In addition, it evaluates potential expression systems for large‐scale enzyme production and analyzes reaction and purification strategies for the synthesis of cyclic dinucleotides to connect fundamental enzymology to bioprocess development for pharmaceutical manufacturing.© 2026 WILEY‐VCH GmbH