engleski

The development of optimal process design of lactol synthesis catalyzed by 2-deoxyribose-5-phosphate aldolase

The examined process is a two-step aldol reaction catalyzed by the genetically modified 2- deoxyribose-5-phosphate aldolase (DERA, E.C. 4.1.2.4) in which the acceptor substrate chloroacetaldehyde (1) reacts with the donor substrate acetaldehyde (2) and gives an intermediate aldehyde (3) that subsequently reacts with a second donor molecule of 2 and results with the key product lactol (4), a valuable chiral synthon for the common statin- type side chain of a cholesterol-lowering drug. The main drawbacks of this process are the enzyme deactivation in the presence of substrates 1 and 2 and the negative impact of product 3 on the enzyme’s stability. Therefore it is essential to develop an effective process for large-scale production, and thus an efficient reactor mode, to diminish the present enzyme deactivation. To successfully achieve it, modeling of reaction kinetics plays an important role. Based on experimentally determined kinetic parameters of the DERA-catalyzed aldol reaction mathematical models of different reactor modes were developed. The models include the negative impact of all aldehydes on the enzyme stability, which were experimentally determined by measuring the enzyme deactivation in different aldehyde (1, 2, or 3) concentrations. In this study three different reactor modes were examined: batch, fed-batch and continuous membrane reactor, and by changing the initial conditions of those, the model simulations were obtained. The optimal process design was proposed based on calculated productivity and biocatalyst consumption.

optimization ; DERA ; statin ; mathematical modelling

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