Mihali Troco K, Kellmann Ralf, Neilan Brett A
School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
BMC Biochem. 2009 Mar 30;10:8. doi: 10.1186/1471-2091-10-8.
Saxitoxin and its analogues collectively known as the paralytic shellfish toxins (PSTs) are neurotoxic alkaloids and are the cause of the syndrome named paralytic shellfish poisoning. PSTs are produced by a unique biosynthetic pathway, which involves reactions that are rare in microbial metabolic pathways. Nevertheless, distantly related organisms such as dinoflagellates and cyanobacteria appear to produce these toxins using the same pathway. Hypothesised explanations for such an unusual phylogenetic distribution of this shared uncommon metabolic pathway, include a polyphyletic origin, an involvement of symbiotic bacteria, and horizontal gene transfer.
We describe the identification, annotation and bioinformatic characterisation of the putative paralytic shellfish toxin biosynthesis clusters in an Australian isolate of Anabaena circinalis and an American isolate of Aphanizomenon sp., both members of the Nostocales. These putative PST gene clusters span approximately 28 kb and contain genes coding for the biosynthesis and export of the toxin. A putative insertion/excision site in the Australian Anabaena circinalis AWQC131C was identified, and the organization and evolution of the gene clusters are discussed. A biosynthetic pathway leading to the formation of saxitoxin and its analogues in these organisms is proposed.
The PST biosynthesis gene cluster presents a mosaic structure, whereby genes have apparently transposed in segments of varying size, resulting in different gene arrangements in all three sxt clusters sequenced so far. The gene cluster organizational structure and sequence similarity seems to reflect the phylogeny of the producer organisms, indicating that the gene clusters have an ancient origin, or that their lateral transfer was also an ancient event. The knowledge we gain from the characterisation of the PST biosynthesis gene clusters, including the identity and sequence of the genes involved in the biosynthesis, may also afford the identification of these gene clusters in dinoflagellates, the cause of human mortalities and significant financial loss to the tourism and shellfish industries.
石房蛤毒素及其类似物统称为麻痹性贝类毒素（PSTs），是神经毒性生物碱，也是麻痹性贝类中毒综合征的病因。PSTs通过独特的生物合成途径产生，该途径涉及微生物代谢途径中罕见的反应。然而，诸如甲藻和蓝细菌等亲缘关系较远的生物似乎使用相同的途径产生这些毒素。对于这种共享的不常见代谢途径如此不寻常的系统发育分布的假设解释包括多系起源、共生细菌的参与和水平基因转移。
我们描述了澳大利亚环状鱼腥藻分离株和美国束丝藻属分离株中假定的麻痹性贝类毒素生物合成簇的鉴定、注释和生物信息学特征，这两种藻类均为念珠藻目的成员。这些假定的PST基因簇跨度约为28 kb，包含编码毒素生物合成和输出的基因。在澳大利亚环状鱼腥藻AWQC131C中鉴定出一个假定的插入/切除位点，并讨论了基因簇的组织和进化。提出了这些生物中导致石房蛤毒素及其类似物形成的生物合成途径。
PST生物合成基因簇呈现出镶嵌结构，即基因明显以不同大小的片段进行了转位，导致在迄今为止测序的所有三个sxt簇中基因排列不同。基因簇的组织结构和序列相似性似乎反映了产生毒素的生物的系统发育，表明基因簇起源古老，或者它们的横向转移也是一个古老的事件。我们从PST生物合成基因簇的特征描述中获得的知识，包括参与生物合成的基因的身份和序列，也可能有助于在甲藻中鉴定这些基因簇，甲藻是导致人类死亡以及给旅游业和贝类产业造成重大经济损失的原因。
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