Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchesterstr. 2, 35394 Gießen, Germany.
Institute for Insect Biotechnology, Justus-Liebig-University of Gießen, Heinrich-Buff-Ring 26-32, 35392 Gießen, Germany.
Toxins (Basel). 2019 Aug 25;11(9):488. doi: 10.3390/toxins11090488.
Animal venoms are promising sources of novel drug leads, but their translational potential is hampered by the low success rate of earlier biodiscovery programs, in part reflecting the narrow selection of targets for investigation. To increase the number of lead candidates, here we discuss a phylogeny-guided approach for the rational selection of venomous taxa, using tarantulas (family Theraphosidae) as a case study. We found that previous biodiscovery programs have prioritized the three subfamilies Ornithoctoninae, Selenocosmiinae, and Theraphosinae, which provide almost all of the toxin sequences currently available in public databases. The remaining subfamilies are poorly represented, if at all. These overlooked subfamilies include several that form entire clades of the theraphosid life tree, such as the subfamilies Eumenophorinae, Harpactirinae, and Stromatopelminae, indicating that biodiversity space has not been covered effectively for venom biodiscovery in Theraphosidae. Focusing on these underrepresented taxa will increase the likelihood that promising candidates with novel structures and mechanisms of action can be identified in future bioprospecting programs.
动物毒液是有前途的新药先导物来源，但由于早期生物发现计划的成功率较低，其转化潜力受到了阻碍，部分原因是调查目标的选择范围较窄。为了增加先导候选物的数量，我们在这里讨论了一种基于系统发育的毒液分类选择方法，以狼蛛（Theraphosidae 科）为例进行了研究。我们发现，以前的生物发现计划优先选择了 Ornithoctoninae、Selenocosmiinae 和 Theraphosinae 这三个亚科，这三个亚科提供了目前公共数据库中几乎所有毒素序列。其他亚科则很少被涉及，如果有的话。这些被忽视的亚科包括几个完整的狼蛛生命树分支，如 Eumenophorinae、Harpactirinae 和 Stromatopelminae 亚科，这表明在 Theraphosidae 中，毒液生物发现的生物多样性空间尚未得到有效覆盖。关注这些代表性不足的分类群将增加在未来生物勘探计划中发现具有新颖结构和作用机制的有前途候选物的可能性。
