ERC Advanced Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, Mainz D-55128, Germany.
National Research Center for Geoanalysis, 26 Baiwanzhuang Dajie, Beijing 100037, China.
Mar Drugs. 2012 Jan;10(1):177-199. doi: 10.3390/md10010177. Epub 2012 Jan 18.
The demosponge Suberites domuncula has been described to contain high levels of a proteinaceous toxin, Suberitine, that displays haemolytic activityIn the present study this 7-8 kDa polypeptide has been isolated and was shown to exhibit also cytotoxic effects on cells of the same species. Addition of retinal, a recently identified metabolite of β-carotene that is abundantly present in S. domuncula was found to reduce both the haemolytic and the cell toxic activity of Suberitine at a molar ratio of 1:1. Spectroscopic analyses revealed that the interaction between β-carotene and Suberitine can be ascribed to a reversible energy transfer reaction. The enzyme that synthesises retinal in the sponge system is the β,β-carotene-15,15'-dioxygenase [carotene dioxygenase]. In order to clarify if this enzyme is the only β-carotene-metabolizing enzyme a further oxygenase had been identified and cloned, the (related) carotenoid oxygenase. In contrast to the dioxygenase, the carotenoid oxygenase could not degrade β-carotene or lycopene in Escherichia coli strains that produced these two carotenoids; therefore it had been termed related-carotenoid oxygenase. Exposure of primmorphs to light of different wavelengths from the visible spectrum resulted after 3 days in a strong upregulation of the dioxygenase in those 3D-cell aggregates that had been incubated with β-carotene. The strongest effect is seen with blue light at a maximum around 490 nm. It is concluded that the toxin Suberitine is non-covalently modified by retinal, the cleavage product from β-carotene via the enzyme carotene dioxygenase, a light inducible oxygenase. Hence, this study highlights that in S. domuncula the bioactive metabolite, retinal, has the property to detoxify its homologous toxin.
海绵亚门纲沙鸡海绵(Suberites domuncula)中含有高水平的蛋白毒素沙鸡海绵素,具有溶血活性。本研究分离出该 7-8 kDa 多肽,并证实其对同种细胞也具有细胞毒性。添加视黄醛(β-胡萝卜素的一种最近被鉴定的代谢产物,在沙鸡海绵中大量存在)可使沙鸡海绵素的溶血和细胞毒性活性降低,摩尔比为 1:1。光谱分析表明,β-胡萝卜素和沙鸡海绵素之间的相互作用可归因于可逆的能量转移反应。在海绵系统中合成视黄醛的酶是β,β-胡萝卜素-15,15'-加氧酶[类胡萝卜素加氧酶]。为了阐明该酶是否是唯一的β-胡萝卜素代谢酶,进一步鉴定并克隆了一种氧合酶,即(相关的)类胡萝卜素氧合酶。与加氧酶相反,类胡萝卜素氧合酶不能在产生这两种类胡萝卜素的大肠杆菌菌株中降解β-胡萝卜素或番茄红素;因此,它被称为相关类胡萝卜素氧合酶。原肠胚暴露于可见光谱的不同波长的光下 3 天后,在与β-胡萝卜素孵育的那些 3D 细胞聚集体中,加氧酶的表达水平显著上调。在 490nm 左右的最大蓝光下,效果最强。结论是,毒素沙鸡海绵素通过酶类胡萝卜素加氧酶,即光诱导的加氧酶,被β-胡萝卜素的裂解产物视黄醛非共价修饰。因此,本研究强调了在沙鸡海绵中,生物活性代谢物视黄醛具有使同源毒素解毒的特性。