Issue 12, 2024

Development of a multi-enzyme cascade for 2′3′-cGAMP synthesis from nucleosides

Abstract

The interest in multi-enzyme cascades for the synthesis of pharmaceutically relevant active ingredients has increased in recent years. Through a smart selection of enzymes, cascades enable multi-step synthesis in a one-pot reaction without the purification of intermediates. In this study, a five-enzyme cascade for the formation of cyclic 2′3′-GMP-AMP (2′3′-cGAMP) from adenosine and guanosine in seven reaction steps was successfully developed. First, the substrate scope of kinases for the phosphorylation of nucleosides and nucleotides was investigated, which were then combined in an enzyme cascade for 2′3′-cGAMP formation from adenosine, guanosine, and polyphosphate. An overall conversion of 57% of the substrates into 2′3′-cGAMP was achieved in relation to the initial guanosine concentration.

Graphical abstract: Development of a multi-enzyme cascade for 2′3′-cGAMP synthesis from nucleosides

Supplementary files

Article information

Article type
Paper
Submitted
01 Feb 2024
Accepted
24 Apr 2024
First published
26 Apr 2024
This article is Open Access
Creative Commons BY license

Catal. Sci. Technol., 2024,14, 3335-3345

Development of a multi-enzyme cascade for 2′3′-cGAMP synthesis from nucleosides

M. Becker, I. Nowak, K. Hildebrand, S. Lütz and K. Rosenthal, Catal. Sci. Technol., 2024, 14, 3335 DOI: 10.1039/D4CY00147H

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