Key result
Biological synthesis of cyclic dinucleotides shortens production time versus chemical methods but limits preparative quantities.
Why the study?
Synthesis of cyclic dinucleotides in preparative quantities remains challenging due to low yields and complex routes in chemical synthesis, and low product titers and process stability in enzymatic synthesis.
Biological synthesis of cyclic dinucleotides offers advantages over chemical synthesis, such as shorter synthesis time and avoiding complex protective group chemistry, though producing preparative quantities remains a challenge.
Cyclic dinucleotides (CDNs) are widely used secondary signaling molecules in prokaryotic and eukaryotic cells. As strong agonists of the stimulator of interferon genes, they are of great interest for pharmaceutical applications. In particular, cyclic-GMP-AMP and related synthetic CDNs are promising candidates in preclinical work and even some in clinical phase 1 and 2 studies. The comparison of chemical and biocatalytic synthesis routes elucidated that biological CDN synthesis offers some advantages, such as shorter synthesis time, avoiding complex protective group chemistry, and the access to a new spectrum of CDNs. However, the synthesis of CDNs in preparative quantities is still a challenge, since the chemical synthesis of CDNs suffers from low yields and complex synthetic routes and the enzymatically catalyzed synthesis is limited by low product titers and process stability. We aim to review the latest discoveries and recent trends in chemical and biocatalytic synthesis of CDNs with a focus on the synthesis of a huge variety of CDN derivatives. We furthermore consider the most promising biotechnological processes for CDN production by evaluating key figures of the currently known processes.
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Bartsch et al. (2021) reported a review. Biocatalytic synthesis of cyclic dinucleotides vs. Chemical synthesis was evaluated. Biological synthesis of cyclic dinucleotides offers advantages over chemical synthesis, such as shorter synthesis time, though producing preparative quantities remains a challenge.
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