Use of 2-deoxyribose-5-phosphate aldolase for the synthesis of precursors of pharmacologically relevant compounds

ROMINA FERNANDEZ VARELA; ANA LAURA VALINO; EMAN ABDELRAHEEM; ULF HANEFELD; ADOLFO IRIBARREN; ELIZABETH LEWKOWICZ

Graz

Simposio; XV Simposio Internacional de Biocatalisis y Biotransformaciones (BIOTRANS 2021); 2021

Universidad de Graz

In recent years, alternative processes involving enzymes or microorganisms as biocatalysts have been applied for the synthesis of pharmaceutical, industrial and agricultural chemicals, demonstrating the advantages that biocatalysis has over traditional chemical procedures. Aldol additions biocatalyzed by aldolases can yield enantiomerically pure products from non-chiral substrates. Particularly, in our laboratory, we identified microorganisms with 2-deoxiribose-5-phosphate aldolase (DERA; EC 4.1.2.4) activity useful for preparing intermediates for antivirals and anticholesteloremic drugs synthesis (Figure 1). The natural reaction of DERA is the aldol addition between acetaldehyde and glyceraldehyde-3-phosphate (G3P) generating deoxyribose-5-phosphate (DR5P). DR5P can be used as intermediate in the preparation of deoxynucleosides, compounds widely used as antivirals drugs. Another important characteristic of this enzyme is its ability to catalyze a double aldol addition affording 2,4,6-trideoxyhexoses. These compounds are intermediates in the synthesis of statins, drugs used to control blood cholesterol levels. However, DERA is inhibited at high aldehyde concentrations, which is a problem for large-scale reactions. To solve this drawback, an acetaldehyde resistant Pectobacterium atrosepticum strain, has been selected. This enzyme has been cloned, expressed and genetically modified to improve its catalytic efficiency. Employing recombinant DERA whole cells, the complete conversion to DR5P using G3P as substrate was obtained. In addition, when acetaldehyde was used as donor and acceptor, the corresponding 2,4,6-trideoxyhexose was obtained in 50% yield