Nevertheless, several challenges remained to be addressed for the biocatalytic synthesis of Se-containing nucleosides using NPs. These include the poor solubility of the free Se-nucleobases in water, which has so far restricted substrate loading to approximately 1 mM. Furthermore, low substrate conversion was observed, indicating that the reaction equilibria of these reactions might be unfavorable. Additionally, prolonged reaction times have been shown to cause unwanted side reactions such as oxidation and deselenation of the starting material, resulting in heavy losses of the targeted product.