Production of Modified Nucleosides in a Continuous Enzyme Membrane Reactor

Area of Science:

• Biocatalysis and Enzyme Engineering
• Organic Synthesis
• Pharmaceutical Chemistry

Background:

• Nucleoside analogues are crucial for treating viral infections and cancers.
• Traditional chemical synthesis methods are often supplemented by enzymatic approaches.
• High biocatalyst production costs limit the feasibility of enzymatic synthesis.

Purpose of the Study:

• To validate the application of continuous enzyme membrane reactors (EMRs) for nucleoside synthesis.
• To assess the efficiency of EMRs in one-pot transglycosylation reactions for natural and dihalogenated nucleosides.
• To evaluate the cost-effectiveness and downstream processing advantages of EMRs compared to batch reactions.

Main Methods:

• Utilized continuous enzyme membrane reactors (EMRs) for enzymatic synthesis.
• Employed one-pot transglycosylation reactions for producing 2'-deoxyadenosine and dihalogenated nucleoside analogues.
• Monitored product yield, conversion rates, and operational stability over extended periods.

Main Results:

• Achieved continuous production of 2'-deoxyadenosine with >90% yield over 55 days.
• Synthesized dihalogenated nucleosides (2,6-dichloropurine-2'-deoxyribonucleoside and 6-chloro-2-fluoro-2'-deoxyribonucleoside) with high conversion.
• Demonstrated significantly higher product yield per enzymatic unit in EMRs compared to batch processes.

Conclusions:

• EMRs provide a viable continuous synthesis method for nucleosides, overcoming limitations of batch enzymatic reactions.
• The integrated biocatalyst separation in EMRs reduces overall biocatalyst costs and simplifies downstream processing.
• This technology enhances the economic feasibility and efficiency of producing valuable nucleoside analogues for therapeutic applications.