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221 explored the effect of the ncAA incorporation at 11 positions within the active site of a bacterial P450 (CYP102A1) on the regioselectivity for the hydroxylation of ( S )-ibuprofen methyl ester and (+)-nootkatone, and discovered that substituting Leu75 in with p -aminophenylalanine (pAF) significantly enhanced regioselectivity toward the oxidation at position C2′ of ( S )-ibuprofen methyl ester