Microbial preparation of guanosine analogues

ROSARIO MEDICI, JULIETA PANERO, VALERIA RODANO, JAVIER M. MONTSERRAT, LUIS E. IGLESIAS, ELIZABETH S. LEWKOWICZ, ADOLFO M. IRIBARREN

Delft

Congreso; VII Simposio Internacional de Biocatalisis y Biotransformaciones (BIOTRANS 2005); 2005

Universidad de Delft

2,6-Diaminopurine nucleosides are frequently used as pharmaceutical drugs and as guanine nucleoside prodrugs, against cancer and viral diseases. These compounds can be prepared in high yields by transglycosylation using bacterial whole cells as biocatalysts. The enzymes involved in this reaction belong to the transferase class, like nucleoside phosphorylases (NPs). This biotransformation, which uses a pyrimidine nucleoside as the sugar donor and a purine base as an acceptor molecule, is being applied in our laboratory for the synthesis of nucleosides of interest . In contrast, the preparation of guanine nucleosides presents some difficulties due to the low solubility of guanine in the reaction conditions. It is well known that mammalian and bacterial adenosine deaminase (ADA) can be used for the hydrolysis of adenosine analogues . Therefore, we searched bacteria that could synthesise guanosine from 2,6-diaminopurine ribonucleoside, obtained by the method above described, since the corresponding base is more soluble . The bacteria used as the biocatalysts in both biotransformations were selected by a screening of our cell collection.