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

Area of Science:

• Biotechnology and Biochemistry
• Enzymology and Biocatalysis
• Immunology and Pharmaceutical Sciences

Background:

• Cyclic GMP-AMP synthase (cGAS) is a key enzyme in innate immunity, with its immunological roles and catalytic mechanisms extensively studied.
• The potential of cGAS as a biocatalyst for synthesizing the second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP) is largely underexplored.

Purpose of the Study:

• To provide a comprehensive biotechnological perspective on cGAS, focusing on its potential as a biocatalyst.
• To review cGAS' enzymatic and structural characteristics, substrate promiscuity, homologs, and engineered variants relevant to biocatalysis.
• To assess expression systems and reaction engineering strategies for scalable 2'3'-cGAMP production.

Main Methods:

• Literature review of published studies on cGAS.
• Analysis of cGAS enzymatic and structural features, including substrate promiscuity and engineered variants.
• Examination of reported expression systems for cGAS production and assessment of scalability.
• Review of reaction engineering strategies for 2'3'-cGAMP synthesis, production, and purification.

Main Results:

• cGAS possesses enzymatic and structural features suitable for biocatalysis.
• Various expression systems have been reported, with potential for scalable cGAS production.
• Established reaction engineering and purification methods exist for 2'3'-cGAMP synthesis.

Conclusions:

• cGAS is a promising biocatalyst for the efficient synthesis of 2'3'-cGAMP.
• This review bridges fundamental enzymology with applied bioprocessing for cGAS.
• Potential applications for cGAS-derived 2'3'-cGAMP include immunotherapy and vaccine adjuvants in the pharmaceutical industry.