Whole cell-catalyzed synthesis of antiviral nucleosides

ELIZABETH S. LEWKOWICZ, MARÍA C. ROGERT, SILVIA PORRO, AND ADOLFO M. IRIBARREN

madrid

Congreso; 10 º Congreso Europeo de Biotecnología; 2001

Sociedad Europea de Biotecnología

Nucleoside analogues have been extensively used in cancer and antiviral therapies as monomers and, more recently, as building blocks for antisense strategies. Traditionally, nucleosides were prepared by various chemical methods which often involved difficult, inefficient and time-consuming multistage processes. Enzymatic preparations of both natural and unnatural nucleosides have been reported using nucleosides phosphorylases but these processes, in contrast to the whole cell-catalyzed procedure, have the disadvantage of laborious scale-up. Recently, we have demonstrated the high efficiency of E. coli BL21 in the synthesis of adenosine from uridine and adenine1. This work describes the application of that microorganism in the preparation of several adenine and hypoxanthine sugar modified nucleosides (deoxy-, dideoxy- and arabine- ones) Optimal conditions for microbial production of these compounds starting from the corresponding uracil or thymine analogues were determined after the analysis of several experimental parameters such as time, temperature, base: nucleoside ratio and amount of biocatalyst