engleski

Mathematical modelling of lactol synthesis catalyzed by 2-deoxyribose-5-phosphate aldolase

The kinetics of enantioselective production of a valuable chiral synthon for the common statin- type side chain of a cholesterol-lowering drug was studied. The examined process is a two-step aldol reaction catalyzed by the enzyme 2- deoxyribose-5-phosphate aldolase (DERA, E.C. 4.1.2.4) in which the acceptor substrate chloroacetaldehyde reacts with the donor substrate acetaldehyde and gives an intermediate aldehyde, which subsequently reacts with a second donor acetaldehyde molecule and results with the key product lactol (Figure 1). A side reaction of the sequential two-step acetaldehyde self- addition also occurs (Figure 2). In order to find the optimal DERA concentration for obtaining the highest selectivity, several reactions were performed in a batch reactor with same initial substrate concentrations and different initial DERA concentrations. The kinetics of all reactions were determined using the method of initial rates and were described by Michaelis- Menten kinetic models. The kinetic parameters of the proposed models were estimated by nonlinear regression analysis using simplex or least squares method. Based on the kinetic results, mathematical models were developed for the lactol synthesis with selectivity-optimal DERA concentration and were validated in a batch reactor. The noted enzyme deactivation was described with second-order kinetics.

mathematical modelling, lactol, DERA, biocatalysis

Project CARBAZYMES - This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635595.