Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase

Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase

Blog Article

SMART GINKGO The biosynthetic enzyme, ForT, catalyses the formation of a C-C bond between 4-amino-1H-pyrazoledicarboxylic acid and MgPRPP to produce a C-nucleoside precursor of formycin A.The transformation catalysed by ForT is of chemical interest because it is one of only a few examples in which C-C bond formation takes place via an electrophilic substitution of a small, aromatic heterocycle.In addition, ForT is capable of discriminating between the aminopyrazoledicarboxylic acid and an analogue in which the amine is replaced by a hydroxyl group; a remarkable feat given the steric and electronic similarities of the two molecules.Here we report biophysical measurements, structural biology and quantum chemical calculations that provide a detailed molecular picture of ForT-catalysed C-C bond formation and the conformational changes that are coupled to catalysis.

Our findings set the scene for employing engineered ForT variants in the biocatalytic production ALOE SHAVE CREAM DUSK of novel, anti-viral C-nucleoside and C-nucleotide analogues.