engleski

Selection of optimal process design in the synthesis of statin intermediate

Production of the statin precursor (4) from chloroacetaldehyde and acetaldehyde in the reaction catalyzed by 2-deoxyribose-5-phosphate aldolase (DERA) is highly investigated (Figure 1). The main drawback of this process is enzyme deactivation in the presence of substrates ; i.e. acetaldehyde and chloroacetaldehyde. Intermediate (3) in the lactol (4) synthesis catalyzed by DERA, also exhibits negative impact on DERA stability. Hence, the choice of effective process design is of crucial importance to minimize enzyme deactivation. This will lead to the significant improvement of this process. To accomplish this it is necessary to find most effective reactor operation mode. In developing enzyme-catalyzed reaction for large-scale production, modeling of the reaction kinetics plays an important role. Figure 1. The reaction scheme of the acetaldehyde and chloroacetaldehyde aldol addition catalyzed by DERA Based on experimentally determined kinetic parameters of all reactions included in lactol (4) synthesis catalyzed by DERA from Thermotoga maritima, mathematical models in different reactor modes were developed in this work. Models also include enzyme deactivation by all compounds that have negative impact on its stability. This was determined experimentally by measuring dependence of enzyme deactivation in the presence of different concentration of aldehydes. Simulations by model were done by changing the initial conditions in different reactor modes ; i.e. batch, fed-batch and continuous. Based on calculated productivity and biocatalyst consumption, the optimal process design was proposed.

statin precursor, aldolase

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