Abstract
The bi-enzymatic synthesis of the antiviral drug vidarabine (arabinosyladenine, ara-A), catalyzed by uridine phosphorylase from Clostridium perfringens (CpUP) and a purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP), was re-designed under continuous-flow conditions. Glyoxyl–agarose and EziGTM1 (Opal) were used as immobilization carriers for carrying out this preparative biotransformation. Upon setting-up reaction parameters (substrate concentration and molar ratio, temperature, pressure, residence time), 1 g of vidarabine was obtained in 55% isolated yield and >99% purity by simply running the flow reactor for 1 week and then collecting (by filtration) the nucleoside precipitated out of the exiting flow. Taking into account the substrate specificity of CpUP and AhPNP, the results obtained pave the way to the use of the CpUP/AhPNP-based bioreactor for the preparation of other purine nucleosides.
Highlights
The use of biocatalysis in multiple industrial sectors is rapidly expanding due to the several benefits that it offers over traditional chemo-catalytic methods
We focused our attention on the study of the flow biocatalyzed transglycosylation reaction to obtain nucleoside analogues of pharmaceutical interest, such as vidarabine
With the aim to fully exploit the potential of the target biocatalyzed reaction in flow, we carried out a study on the co-immobilization of AhPNP and CpUP on two hydrophilic supports, i.e., glyoxyl–agarose (GA) and EziGTM 1 (Opal) [19,20], which involve a different binding chemistry between the enzymes and the support (Scheme 1)
Summary
The use of biocatalysis in multiple industrial sectors is rapidly expanding due to the several benefits that it offers over traditional chemo-catalytic methods. Enzyme-catalyzed reactions are selective, safe, and environmentally friendly, meeting the increasing demand of industry for more efficient and sustainable processes [1,2]. Low productivity and difficult product downstream are still the most often encountered bottlenecks in biocatalysis, which limit the implementation of enzymatic processes in industry [3]. Flow processing has the potential to accelerate heterogeneous biotransformations due to biocatalyst high local concentration and enhanced mass transfer, making large-scale production more economically feasible in small equipment, with a substantial decrease in reaction time and improvement in space–time yield. A further advantage of flow reactors is that their configuration can be customized to meet the specific requirements of the biotransformation
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