Probing batch and continuous flow reactions in organic solvents: Granulicella tundricola hydroxynitrile lyase (GtHNL)

The authors assessed different reactor operation modes for the enzymatic hydrocyanation of benzaldehyde to (R)-mandelonitrile. For this, the enantioselective Granulicella tundricola hyroxynitrile lyase (GtHNL) was immobilized on Celite R-633 and deployed in a batch-wise operated reaction vessel (BR), a batch-wise operated rotating bed reactor (RBR), and a continuously operated packed bad flow reactor (CFR). In terms of specific reaction rates [mmol/min/g] the BR was outperformed by the RBR by a factor of 1.7 and by the CFR by a factor of 2-3.

Furthermore, the authors report a superior (65-fold improved) space-time yield for the CFR system. Conversely, based on the parameters used for these calculations, the CFR only processes a total of 0.1 mL/min, which means that it would take 900 min (15 h) to process the same reaction volume (90 mL) that was successfully processed by the RBR in only 4 h.

This ambivalence between different performance metrics is mainly due to the fact that the scales of the model reactors representing different operation modes were vastly different: BR (2 mL), RBR (90 mL), CFR (1 mL). Despite this inhomogeneity in the experimental setup, this study shows how valuable it is to investigate and identify the most profitable reactor and operation mode for the practical implemenation of (bio)catalytic applications.

However, to do so, it requires a combined consideration of multiple performance parameters as they inform about different critical aspects of the synthetic process: conversion [%], selectivity [%], isolated yield [%], productivity [g/h], space-time-yield [g/h/L], product titer [g/L], catalyst-specific productivity [kg/g]. Only by accounting for all these factors and their practical implications, the economically most viable strategy can be found.

Highlights:

• "The reaction was scaled up to a 42 times larger reaction mixture volume, utilising a rotating bed reactor (SpinChem, Sweden)."
• “Nearly complete conversion and high enantioselectivity were achieved in both BR and RBR systems with tightly packed enzyme”