Enzymatic skeletal editing reaction forming the 1,3,5-triazine core during biosynthesis of the anticancer nucleoside analogue 5-azacytidine

Nature Catalysis, Published online: 07 September 2026; doi:10.1038/s41929-026-01611-x Despite decades of clinical use, the biosynthetic origin of 5-azacytidine remained unknown. Now the responsible gene cluster is identified, revealing enzymes that convert guanosine triphosphate into a triazine nucleobase through rare skeletal editing and unconventional thiamine-dependent chemistry.