In addition to anchoring artificial metal center on a protein, researchers like Frances Arnold also focused on changing the native environment of natural metal cofactor. Due to the protein context in which the metal catalytic center located, ArMs have a large sequence space to evolve to meet different demands on substance specificity and regio- and enantioselectivity. Directed evolution was used to tailor the catalytic capacity and repurpose the enzyme function. Mostly based on native porphyrin-metal cofactor, Arnold's lab has developed many ArMs has unique ArMs to catalyze regioselective and/or enantioselective Carbon-Boron bond formation, carbene insertion, and aminohydroxylation by evolving the sequence context of the corresponding ArMs.