Highly selective hydroxylation of gaseous alkanes at the terminal position by wild-type CYP153A33†

In the direct hydroxylation of C–H bonds by cytochrome P450s, their regioselectivities between primary and secondary carbons depend strongly on their C–H bond-dissociation energies. Thus, selective hydroxylation at the terminal position is a challenging task because of its low reactivity compared with internal positions. On the other hand, CYP153A33 can hydroxylate long fatty acids with high regioselectivity at the terminal position. For highly selective hydroxylation of gaseous alkanes at the terminal position, we herein combined CYP153A33 with substrate analog decoy molecules to alter the substrate specificity of the enzyme. Perfluoroacyl amino acids can effectively activate CYP153A33 and facilitate the regioselective hydroxylation of propane at the terminal position to afford 1-propanol (1-propanol/2-propanol = 80/20). In addition, we found that the use of CYP153A33 with decoy molecules also enables the hydroxylation of ethane and methane.