Different biocatalysed strategies in nucleoside chemistry

ROSARIO MEDICI; ELIZABETH LEWKOWICZ; ADOLFO IRIBARREN

Berna

Congreso; Biotrans2009; 2009

Sociedad Europea de Biocatálisis

Modified nucleosides and their bases are a family of widely studied phar-macologically active compounds, which includes antivirals and antitumoral agents. In the last years, new biocatalysed strategies were developed in order to widen the structural diversity of this family and also to prepare phosphate derivatives that are regarded as potential hydrophilic prodrugs. Having these targets in mind, we carried out the search of new biocatalysts for the introduction, modification and transformation of functional groups present in nucleosides or nucleoside precursors. Several screening meth-odologies were developed allowing the selection of whole cells capable of carrying out deamination, hydroxylation, halogenation and phosphoryla-tion reactions: ? Bacterial whole cells belonging to Streptomyces and Pseudomonas genus with haloperoxidase activity on deazapurines, affording 5-bromoindole in 85% yield. ? Arthrobacter oxydans cells with adenosine deaminase (ADA) activity on several 6- and 2,6-substituted nucleosides, producing arabinoguanosine, a well-known antileukemic agent, in 50% yield. ? Bacterial whole cells belonging to the genus Enterobacter y Klebsiella with phosphorylating activity on natural and modified nucleosides. Fludarabine-5?-monophosphate, was obtained under mild conditions.An acid phosphatase from Enterobacter aerogenes was overexpressed in a re-combinant E. coli, affording improved reaction times in the biocatalyzed phosphorylation of sugars and nucleosides.