Serendipitous discovery of Chl d formation from Chl a with papain

Cancer photodynamic therapy (PDT) requires the availability of photosensitizers which have a high efficiency and selectivity for the destruction of tumor cells. Chlorophyll (Chl) a is one of the favorable photosensitizers, because it has a high extinction coefficient in the red light region, where light transmission through the human tissues is very high. However, Chl a had a serious problem that it cannot be dissolved in water, so we tried to prepare water-soluble chlorophyllide a from Chl a by several enzymes, and serendipitously came across a unique formation of Chl d from Chl a when papain was used in aqueous acetone. Similar oxidation was observed in Chl b and pheophytin a, although the reactions were very slow. Our finding will provide insight into the unsolved key question as to the biosynthetic pathway of Chl d via Chl a in a recently found novel cyanobacterium Acaryochloris marina.