Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. A pyrazole-methylating enzyme family that transfers alkyl groups in catalyst-controlled highly selective C-N bond formations to the pyrazole substrate was created using a computational enzyme library design tool. A second, promiscuous enzyme generates non-natural-analogues of the common cofactor S-adenosyl-l-methionine utilizing simple haloalkanes as precursors. These enzymes were combined in a bienzymatic cascade where the cofactor is recycled and only used in catalytic amounts. With this enzymatic system, selective pyrazole alkylation (methylation, ethylation and propylation) was achieved with unprecedented regioselectivities (>99%), regiodivergence and in a first example on preparative scale.