First and second sphere interactions accelerate non-native N-alkylation catalysis by the thermostable, methanol-tolerant B(12)-dependent enzyme MtaC

The corrinoid protein MtaC, which is natively involved in methyl transferase catalysis, catalyzes N-alkylation of aniline using ethyl diazoacetate. Our results show how the native preference of B(12) scaffolds for radical versus polar chemistry translates to non-native catalysis, which could guide selection of B(12)-dependent proteins for biocatalysis. MtaC also has high thermal stability and organic solvent tolerance, remaining folded even in pure methanol.