title: Calyculin: Nature's way of making the sponge-derived cytotoxin.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan. wakimoto@pharm.hokudai.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan. wakimoto@pharm.hokudai.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Egami
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D008387:Marine Toxins; D015394:Molecular Structure; D005810:Multigene Family; D010080:Oxazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D008387:Marine Toxins; D010080:Oxazoles; D010455:Peptides; C059041:calyculin A; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2