Abstract
Covering: up to 2015.Calyculin A is a major cytotoxic compound isolated from the Japanese marine sponge Discodermia calyx. Its potent cytotoxicity is attributable to the specific inhibition of protein phosphatases 1 and 2A, as in the case of okadaic acid and the microcystins. Its chemical structure is well-designed not only for enzyme inhibition but also for higher membrane permeability in order to impart its potent cytotoxicity. The biosynthetic gene cluster of this densely functionalized polyketide and nonribosomal peptide hybrid molecule was recently identified from the sponge-microbe association. The producer organism and the dynamic bioconversion process were also revealed. In this highlight, we focus on the recent studies addressing nature's design and biogenesis of the sponge-derived cytotoxin, calyculin A.
Highlights
The marine sponge Discodermia calyx inhabits relatively shallow water in the central to southern areas of Japan
The natural source of the calyculins is not limited to D. calyx, as other sponge species contain calyculin derivatives, such as the calyculinamides from the New Zealand sponge Lamellomorpha strongylata,[5] the clavosines (10) from the Palauan sponge Myriastra clavosa,[6] geometricin (11) from the Australian sponge Luffariella geometrica,[7] and swinhoeiamide (12) from the Papua aFaculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan
The biosynthetic gene cluster and the producer organism were identi ed in the Japanese marine sponge D. calyx.[9]. This highlight focuses on the biological activity, the biosynthesis, and the producer organism of the calyculins
Summary
This marine sponge was part of the vast collection of Japanese marine organisms amassed by the German biologist Ludwig Doderlein, who was a visiting Professor at the University of Tokyo from 1879–1881, and it was identi ed based on a specimen collected in the Gulf of Sagami, Japan.[1] Almost one hundred years later, Fusetani and co-workers reported that the marine sponge contains a major secondary metabolite, calyculin A (Fig. 1, 1, 0.15% wet weight), showing potent activity in the star sh egg assay.[2] Subsequently, 1 was revealed to have pM range IC50 values against several cancer cell lines and tumor promotion activity, ascribed to the speci c and potent inhibition of protein phosphatases 1 and 2A (PP1 and 2A),[3] thereby rendering it a valuable tool to evaluate intracellular signal transduction. This highlight focuses on the biological activity, the biosynthesis, and the producer organism of the calyculins
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