Collaborative Research: Emergence of terpene cyclization in animals

生物体之间的化学相互作用代表着自然界中一种关键的交流形式，并由不同的小分子阵列来调节。这些分子或化学线索在维持和推动物种多样性和生态系统功能方面起着关键作用。研究团队使用跨学科的方法，探索化合物是如何出现并具有生物功能的问题，重点是了解萜烯的出现--萜烯是昆虫用来抵御敌人和病原体、寻找食物以及吸引或寻找配偶的主要分子家族。该项目整合了计算建模和分子修改，重建了酶的进化，这些酶是昆虫中萜类化学多样性产生的核心。通过他们的研究，研究人员将开发一个综合的经验和理论平台，作为追踪各种蛋白质家族进化的蓝图。该项目具有更广泛的社会和教育影响，包括可能产生用于工业应用的目标酶产品和基因变体，以及将研究成果转化为视觉装置，普通公众将通过弗吉尼亚理工大学和西弗吉尼亚科学博物馆的剧院获得该装置。萜类化合物构成了一大类主要是环状分子，在生物体的化学相互作用中起主要作用。然而，在动物中负责环化和萜类多样性的酶功能的出现仍然是难以捉摸的。研究小组将应用计算和实验方法相结合的方法来确定昆虫萜类多样性背后的关键酶适应--昆虫是物种最丰富的动物谱系。具体地说，该项目定义了激活异戊二磷酸合成酶(IDs)中萜烯环酶(TPS)酶功能的修饰，这些酶参与核心萜烯代谢。研究人员将在不同的昆虫分类群中鉴定和功能表征萜烯环化酶，以评估与这些酶在昆虫中的进化相对应的适应性变化。功能数据将与蛋白质结构分析相结合，以生成精确定位氨基酸残基网络的模型，这将触发入侵检测系统模板上TPS活动的出现。网络模型将被用来构建合成酶文库，并帮助表征萜类环化的突变途径。研究人员还将利用这项研究的数据开发酶进化动力学的综合生物物理模型，定量描述在萜类多样性出现时酶功能的基本转变。总体而言，这一跨学科项目的见解将有助于更好地理解自然界酶和化学多样性重大扩张背后的生物物理原理。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Chemical interactions between organisms represent a key form of communication in nature and is mediated by diverse arrays of small molecules. These molecules or chemical cues serve critical roles in maintaining and driving species diversity and ecosystem functions. Using interdisciplinary methods, the team of investigators explore the question of how chemical compounds emerge and adopt biological functions with a specific focus on understanding the emergence of terpenes - a major family of molecules used by insects to ward off enemies and pathogens, search for food, and attract or seek out mates. Integrating computational modeling and molecular modifications, the project reconstructs the evolution of enzymes that are central to the generation of terpene chemical diversity in insects. Through their study, the investigators will develop an integrated empirical and theoretical platform that will serve as a blueprint for tracing the evolution of various protein families. The project has broader societal and educational impacts, including potential generation of target enzyme products and gene variants for industrial applications and translation of research results into a visual installation, which will be accessible to the general public through theaters at Virginia Tech and the Science Museum of Western Virginia. Terpenes constitute a large class of mostly cyclic molecules with major roles in chemical interactions of organisms. However, the emergence of enzymatic functions responsible for the cyclization and diversity of terpenes in animals has remained elusive. The research team will apply a combination of computational and experimental methods to define key enzymatic adaptations underlying terpene diversity in insects - the most species-rich lineage of animals. Specifically, the project defines modifications that activate terpene cyclase (TPS) enzymatic function in isoprenyl diphosphate synthases (IDS), enzymes involved in core terpene metabolism. Investigators will identify and functionally characterize terpene cyclase enzymes in diverse insect taxa to assess adaptive changes corresponding to the evolution of these enzymes in insects. The functional data will be combined with protein structural analysis to generate models that pinpoint amino acid residue networks, which trigger the emergence of TPS activities on IDS templates. Network models will be used to construct synthetic enzyme libraries and help characterize mutational pathways that underlie terpene cyclization. Investigators will also use data from the study to develop integrated biophysical models of enzyme evolutionary dynamics that quantitatively describe fundamental transitions of enzyme function in the emergence of terpene diversity. Cumulatively, the insights from this interdisciplinary project will lead to an improved understanding of the biophysical principles behind major expansions of enzymatic and chemical diversity in nature.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.