engleski

Modelling of Lactol Oxidation Catalyzed by Oxidoreductases

Statins are the most widely prescribed drugs in the world used for lowering low-density lipoprotein (LDL) cholesterol, because they act as competitive inhibitors of HMG-CoA reductase, a crucial enzyme in the cholesterol biosynthesis. Even though well-established chemical approaches are employed, they are time-consuming and include a vast number of steps. The increasing commercial demand for statins and the requirements for high chemical and stereochemical purity have led to immense efforts for more efficient and economical production of key chiral statin-type side chains. Therefore, biocatalytic strategies are being developed and represent the most attractive alternative, due to the nature of the enzymes to perform high stereoselective attacks under mild conditions. Once the lactol is enzymatically produced, the desired statin-type side chain precursor can be easily obtained upon oxidation of the intermediate lactol to lactone. In this work two different NAD(P)-dependent oxidoreductases were investigated for the lactol oxidation. To make the synthesis economically and practically feasible, the in situ NAD(P)+ coenzyme regeneration was carried out by NAD(P)H oxidase. The stability of all three enzymes was examined in the presence of all aldehyde substrates and products involved in the reaction of lactol production. Based on experimental data the enzymes were kinetically characterized and the developed mathematical models were validated in a batch reactor. Project CARBAZYMES - This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635595.

Statins ; NAD(P)-dependent oxidoreductases ; Stability ; Mathematical modelling

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