Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nat Prod Rep. 2016 Jun 2;33(6):751-60. doi: 10.1039/c5np00123d.
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.
截至 2015 年。卡拉醇 A 是从日本海洋海绵 Discodermia calyx 中分离出来的主要细胞毒素化合物。它具有很强的细胞毒性，这归因于对蛋白磷酸酶 1 和 2A 的特异性抑制，就像岗田酸和微囊藻毒素一样。其化学结构不仅经过精心设计用于酶抑制，而且还具有更高的膜通透性，从而赋予其强大的细胞毒性。该功能丰富的聚酮和非核糖体肽杂合分子的生物合成基因簇最近从海绵-微生物共生体中被鉴定出来。也揭示了产生该物质的生物体和动态生物转化过程。在这篇综述中，我们重点介绍了最近研究天然设计和海绵来源细胞毒素卡拉醇 A 的生物发生的研究。
