An enzymatic activation of formaldehyde for nucleotide methylation

Abstract

The bacterial thymidylate synthase ThyX catalyzes the reductive methylation of deoxyuridylate (dUMP) into deoxythymidylate (dTMP) and requires both folate and flavin for activity. Here, the authors combine biochemical experiments, spectroscopic measurements and flavin synthesis chemistry to show that formaldehyde (CH2O) can replace the natural methylene donor of ThyX in a CH2O-shunt reaction, yielding a carbinolamine intermediate with the reduced flavin coenzyme, and they present the crystal structure of this intermediate.