1867-16-9Relevant academic research and scientific papers
An Engineered Cytidine Deaminase for Biocatalytic Production of a Key Intermediate of the Covid-19 Antiviral Molnupiravir
Birmingham, William R.,Burke, Ashleigh J.,Charnock, Simon J.,Crawshaw, Rebecca,Finnigan, James D.,Green, Anthony P.,Holgate, Gregory M.,Lovelock, Sarah L.,Muldowney, Mark P.,Rowles, Ian,Thorpe, Thomas W.,Turner, Nicholas J.,Young, Carl,Zhuo, Ying,Zucoloto Da Costa, Bruna
supporting information, p. 3761 - 3765 (2022/03/15)
The Covid-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue recently approved as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of an efficient biocatalyst for the production of N-hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs >85 000 turnovers in less than 3 h, operates at 180 g/L substrate loading, and benefits from in situ crystallization of the N-hydroxy-cytidine product (85% yield), which can be converted to Molnupiravir by a selective 5′-acylation using Novozym 435.
