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Insect prophenoloxidase(PPO)is an essential innate immunity protein to induce pathogen into melanization.In Bombyx mori,pro-phenoloxidase-activating enzyme(PPAE)can directly cleave and activate PPO.However,PPO in Manduca sexta cannot be cleaved into active phenoloxidase(PO)by serine proteases unless cofactors are involved,which indicates that PPO activation is complicated.