Biocatalytic oxidase: Batch to continuous

The adoption of more efficient development strategies and manufacturing techniques will be essential for future success in the bio manufacturing sectors. Continuous operation of biocatalytic processes has the potential to offer many advantages over established batch process methodologies. There exist opportunities for improved process control; ease of scale up; minimizing of interruptions in production; reducing reactor size; and economic use of biocatalysts.The Coflore™ Agitated Cell Reactor (ACR) is a dynamically mixed plug flow reactor. The Coflore design employs a patented mixing technique where free moving agitators within each reaction stage promote mixing when the reactor body is subjected to lateral shaking. Multiple discrete (interlinked) reaction cells give good mixing and plug flow, and the design permits the use of slurries and handling of gas/liquid mixtures. The Coflore Agitated Tube Reactor (ATR) is an industrial tube flow reactor for homogenous and two phase fluids. Employing the same mixing principle as the lab scale Coflore ACR, it uses lateral movement to generate mixing and stage separation to prevent back mixing.We describe the application of these continuous plug flow reactors for bioprocess development starting from simple lab scale batch processes; through benchtop plug flow reactors (ACRs); and on to the multi-litre production scale agitated tube reactor (ATR). The presentation will compare the results of an oxidation reaction catalysed by d-amino acid oxidase (DAAO) operated under batch and continuous conditions, and will illustrate how application of the ACR and ATR reactors can facilitate process development.

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► dl-Amino acid is resolved biocatalytically by oxidation of the d-amino acid giving a mixture of l-amino acid and the α-ketoacid using wild-type d-amino acid oxidase.
► Comparisons are made between batch and continuous synthesis.
► Reaction is shown to be mixing sensitive.
► Continuous processing allows increased oxygen transfer into reaction medium.
► Previously un-scalable process shown to be scalable in continuous mode.