Nucleoside analogues are widely used as antiviral and antitumor drugs by blocking the activity of DNA or RNA polymerases. An archaeal enzyme that converts a nucleotide triphosphate (NTP) to a nucleotide monophosphate (NMP)-small molecule (SM) adduct via formation of a NMP-O-R or a NMP-N-R linkage was recently identified in the laboratory. While the biological significance of this activity is unknown, its utility as a potentially inexpensive and bio-friendly method for biomanufacturing nucleoside analog “pro-drugs” is being explored. Ongoing research focuses on determining the efficiency and selectivity of the enzyme reaction by exploring the chemical space of SMs (i.e., sugars, lipids, amino acids) as well as nucleoside analogues (i.e., ddNTPs) that can used by the enzyme as substrates to generate NMP-SM.

References

Galal WC, Pan M, Kelman Z, Hurwitz J: Journal of Biological Chemistry 287: 16209, 2012

Galal WC, et al: Journal of Biological Chemistry 287: 16220, 2012