Biocatalytic synthesis of seleno-, thio- and chloro-nucleobase modified nucleosides by thermostable nucleoside phosphorylases

Abstract

Selenium-containing nucleosides are the building blocks of the Se-nucleic acids useful for structure-and-function study, drug discovery and for targeting nucleic acids and their protein complexes. However, chemical synthesis of these Se-containing nucleosides is labor-intensive and provides low overall yields. Thus, we decided to explore biocatalytic synthesis of the modified nucleosides (such as Se-nucleosides) by employing thermostable nucleoside phosphorylases from thermophilic microorganisms. We were surprised to discover that these enzymes can still recognize the nucleobases containing rather larger atoms, Se vs O atom. These enzymes also showed excellent adaptability to some modified purines with high substrate conversion (up to 97%).