engleski

Kinetic characterization of enzymes in a multi-enzyme cascade reaction for the synthesis of statin side-chain precursors

Statins are a class of medicine that lower the level of low-density lipoprotein (LDL) cholesterol in blood. This can reduce the risk of cardiovascular disease and prevent heart attack and stroke. The modern requirements for stereochemical purity have created new challenges for industrial preparation of statins. One of the ways to achieve the required enantio- and diastereopurities is the use of biocatalysis. In this work, a cascade reaction with three enzymes was investigated for the synthesis of statin side-chain precursors. The first enzyme in this cascade is alcohol dehydrogenase used for the oxidation of an alcohol to aldehyde. The second enzyme is NADH oxidase used for coenzyme regeneration and the third one is deoxyribose-phosphate aldolase for the aldol addition of acetaldehyde and the corresponding aldehyde. All three enzymes were kinetically characterized in order to develop a mathematical model. Mathematical modeling plays an important part in developing processes involving biocatalysts. In order to reach industrial application, each enzyme and reaction system have to be kinetically characterized. Modelling increases our knowledge about the process, since it enables simulation of different reaction courses. This offers better understanding of the effect that different variables have on the equilibrium, conversion etc.

cascade reaction, kinetic characterization, statin side-chain precursors

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