Protein cages can serve as bioinorganic molecular templates for functionalizing
metal compounds to regulate cellular signaling. We succeeded in developing a
photoactive CO-releasing system by constructing a composite of ferritin (Fr)
containing manganese-carbonyl complexes. When Arg52 adjacent to Cys48 of Fr is
replaced with Cys, the Fr mutant stabilizes the retention of 48 Mn-carbonyl
moieties, which can release the CO ligands under light irradiation, although
wild-type Fr retains very few Mn moieties. The amount of released CO is
regulated by the extent of irradiation. This could reveal an optimized dose for
cooperatively activating the nuclear factor κB (NF-κB) in mammalian cells and
the tumor necrosis factor α (TNF-α). These results suggest that construction
of a CO-releasing protein cage will advance of research in CO biology.