A novel N-oxygenase-coated core-shell nano particle was generated through the coassembly of poly(4-vinylpyridine) (P4VP) and arylamine N-oxygenase CmlI. The resulting enzyme-hybridized particles, P4VP-CmlI, showed excellent catalytic activities on the oxidation of two arylamine substrates, i.e., p-aminophenol (pAP) and p-aminobenzoic acid (pABA), using a surrogate redox system or a peroxide shunt as co-oxidants. In comparison with the free enzyme, P4VP-CmlI particles exhibited a significantly enhanced catalytic efficiency when using pyridine nucleotide (NADH) and proper redox mediators. Products at different oxygenation stages were observed. On the contrary, the activity of the enzyme containing nanoparticles was very similar to the free enzyme when using the peroxide shunt. The enhanced catalytic efficiency of the P4VP-CmlI assemblies is attributed to a more efficient electron delivery.