BIOSYNTHETIC-STUDIES OF BREVETOXINS, POTENT NEUROTOXINS PRODUCED BY THE DINOFLAGELLATE GYMNODINIUM-BREVE
BIOSYNTHETIC-STUDIES OF BREVETOXINS, POTENT NEUROTOXINS PRODUCED BY THE DINOFLAGELLATE GYMNODINIUM-BREVE
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DOI：
10.1021/ja00198a039
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发表时间：
1989-08-02
影响因子：
15
通讯作者：
ZAGORSKI, MG
中科院分区：
文献类型：
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作者：
LEE, MS;QIN, GW;ZAGORSKI, MG
短甲藻（Ptychodiscus brevis）的大量繁殖，俗称“赤潮”，导致佛罗里达海岸和墨西哥湾沿岸大量鱼类死亡、软体动物污染和人类食物中毒。导致这些现象的来自短G. breve的毒素是短链毒素(BTX's)，这是一组具有多环转融合任一环的强效神经毒素，其可能使可兴奋膜的钠通道去极化。 BTX-B，C50H70O14是第一个结构被阐明的神经毒素，它具有前所未有的结构，由6/6/6/7/7/6/6/8/6/6/6个醚环以梯状方式融合而成。这些毒素的另一个成员，BTX-A，C49H70O13，具有另一个由转融合的 5/8/6/7/9/6/6/6 醚环组成的显着结构。尽管 BTX-B 和 BTX-A 的碳骨架不同，但两者均由带有甲基取代基的多氧合单碳链组成。这与聚酮化合物生物合成一致，即乙酸盐单元与源自S-腺苷甲硫氨酸或丙酸盐的甲基的缩合。使用[1-13C]-和[2-13C]乙酸钠以及[甲基-13C]甲硫氨酸的标记实验表明，BTX-B和BTX-A的标记模式相似，并且短尾毒素的生物合成不是简单的聚酮化合物起源。这些标记研究表明柠檬酸循环参与了BTX-B和BTX-A的生物合成，其参与程度异常高。此外，CO2 以独特的方式参与 BTX-B 和 BTX-A 的 C-1 生物合成。
Blooms of the dinoflagellate Gymnodinium breve (Ptychodiscus brevis) commonly known as "red tide" have led to massive fish kills, mollusk contamination, and human food intoxications along the Florida coast and the Gulf of Mexico. The toxins from G. breve responsible for these phenomena are the brevetoxins (BTX''s), a group of potent neurotoxins with polycyclic trans-fused either rings which presumably depolarize the sodium channels of the excitable membranes. BTX-B, C50H70O14, the first of these neurotoxins whose structure was elucidated, has an unprecedented structure consisting of 6/6/6/7/7/6/6/8/6/6/6 ether rings trans-fused in a ladder-like manner. Another member of these toxins, BTX-A, C49H70O13, has another remarkable structure consisting of trans-fused 5/8/6/7/9/6/6/6 ether rings. Although the carbon skeletons of BTX-B and BTX-A are different, both consist of a single carbon chain that is polyoxygenated with methyl substituent groups. This is consistent with polyketide biosynthesis, i.e., condensation of acetate units with the methyl groups originating from either S-adenosylmethionine or propionate. Labeling experiments using sodium [1-13C]- and [2-13C]acetate and [methyl-13C]methionine demonstrate that the labeling patterns of BTX-B and BTX-A are similar and that the biosynthesis of brevetoxins is not of simple polyketide origin. These labeling studies suggest that the citric acid cycle is involved in the biosynthesis of BTX-B and BTX-A, the degree of its involvement being unusually high. Furthermore, CO2 participates in a unique manner in the biosynthesis of C-1 of BTX-B and BTX-A.