Biosynthetic route towards saxitoxin and shunt pathway.
Biosynthetic route towards saxitoxin and shunt pathway.
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DOI：
10.1038/srep20340
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发表时间：
2016-02-04
影响因子：
4.6
通讯作者：
Yotsu-Yamashita M
中科院分区：
文献类型：
--
作者：
Tsuchiya S;Cho Y;Konoki K;Nagasawa K;Oshima Y;Yotsu-Yamashita M
蛤蚌毒素是由蓝藻和鞭毛藻产生的麻痹性贝类毒素之一，是最有效的电压门控钠通道阻滞剂。最近，在这些微生物中报道了推测的PSTs生物合成基因。我们之前合成了遗传预测的生物合成中间体，Int-A ‘和Int-C ’ 2，以及未基于基因预测的Cyclic-C '，并在产毒蓝藻Anabaena circinalis （TA04）和鞭毛藻Alexandrium tamarense （Axat-2）中鉴定出它们。本研究检测了15n标记的中间体在A. circinalis （TA04）的pst （C1和C2）中的结合。使用高分辨率lc /MS表示从Int-A ‘到Int-C ’ 2，从Int-C ' 2到cycle - c ‘，以及从Int-A ’和Int-C ' 2到C1和C2的转换。然而，Cyclic-C '不转化为C1和C2，主要在细胞外培养基中检测到。这些结果表明，Int-A ‘和Int-C ’ 2是PSTs的真正前体，但Int-C ' 2部分转化为Cyclic-C '，这是一种排泄到细胞外的分流产物。本文首次直接论证了石蜡毒素的生物合成途径及其分流途径。
Saxitoxin, the most potent voltage-gated sodium channel blocker, is one of the paralytic shellfish toxins (PSTs) produced by cyanobacteria and dinoflagellates. Recently, putative biosynthetic genes of PSTs were reported in these microorganisms. We previously synthesized genetically predicted biosynthetic intermediates, Int-A’ and Int-C’2, and also Cyclic-C’ which was not predicted based on gene, and identified them all in the toxin-producing cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2). This study examined the incorporation of 15N-labeled intermediates into PSTs (C1 and C2) in A. circinalis (TA04). Conversions from Int-A’ to Int-C’2, from Int-C’2 to Cyclic-C’, and from Int-A’ and Int-C’2 to C1 and C2 were indicated using high resolution-LC/MS. However, Cyclic-C’ was not converted to C1 and C2 and was detected primarily in the extracellular medium. These results suggest that Int-A’ and Int-C’2 are genuine precursors of PSTs, but Int-C’2 converts partially to Cyclic-C’ which is a shunt product excreted to outside the cells. This paper provides the first direct demonstration of the biosynthetic route towards saxitoxin and a shunt pathway.