engleski

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

The aldol reaction has long been recognized as one of the most powerful methods of forming useful carbon-carbon bonds. Aldolases, a group of naturally occurring enzymes that catalyze in vivo aldol reactions, are capable of exhibiting high regio- and stereoselectivity under mild conditions, and therefore are an interesting alternative to chemical aldol reactions. The enzyme 2-deoxyribose-5-phosphate aldolase (DERA, E.C. 4.1.2.4) is the only known member of the acetaldehyde-dependent aldolase family, and is the only aldolase known to accept three aldehydes in a sequential and stereo-selective manner during an aldol reaction without the use of any cofactors. By using achiral substrates, like chloroacetaldehyde (1) and acetaldehyde (2), DERA catalyzes the sequential aldol addition which results with an enantiomerically pure lactol. The obtained molecule is a valuable chiral synthon of HMG-CoA reductase inhibitor, collectively known as statin, used for the production of world’s top-selling cholesterol-lowering drugs. When finding the most cost-effective mode for the lactol synthesis, especially for further industrial use, it is of great importance to understand the mechanisms and kinetics of enzyme systems, which can be achieved by applying mathematical modelling techniques. Therefore, the purpose of this work was to characterize the enzyme and to develop a mathematical model of the DERA-catalyzed reaction for synthesis of statin- type side chain that can be further used as a useful tool in designing a suitable reaction system.

mathematical modeling ; DERA ; aldol addition ; biocatalysis

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