Kobayashi et al. isolated callystatin A in 1997 from the marine sponge Callyspongia truncata using acetone extraction. This marine sponge was discovered near the Goto Islands of the Nagasaki Prefecture in Japan. Kobayashi also reported the isolation of callystatin A from another marine sponge Stelletta sp. and an unidentified marine tunicate, both of which were collected at the same site as Callyspongia truncata. It is possible that there is a symbiotic relationship among these microorganisms which can explain their biosynthesis of callystatin A.
The leptomycin family of molecules that callystatin belongs to includes several well-known molecules with cytotoxic properties. such as leptomycins A and B, anguinomycins A and B, kazusamycin, and leptofuranins A-D. All of these molecules were isolated from various strains of Streptomyces sp. and share a common structural motif consisting of a terminal α,β-unsaturated lactone group attached to a long unsaturated fatty acid chain which includes two diene systems separated by two sp-hybridized carbons. It is believed that this highly conserved structural motif is important for biological target recognition with the α,β-unsaturated lactone moiety serving as the pharmacophore of the molecule.