Collaborative Research: Emergence of terpene cyclization in animals

合作研究：动物体内萜烯环化的出现

• 批准号: 1920925
• 负责人: Dorothea Tholl
• 金额: $ 76.52万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1920925&HistoricalAwards=false
• 关键词: Collaborative; Research; Emergence; terpene; cyclization

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.

生物体之间的化学相互作用代表了自然界沟通的一种关键形式，并由不同的小分子阵列介导。 这些分子或化学线索在维持和驱动物种多样性和生态系统功能方面发挥着关键作用。研究小组利用跨学科方法，探索化合物如何出现并发挥生物功能的问题，特别关注了解萜烯的出现。萜烯是昆虫用来抵御天敌和病原体、寻找食物、吸引或寻找配偶的主要分子家族。该项目结合计算模型和分子修饰，重建了酶的进化，这些酶对于昆虫中萜烯化学多样性的产生至关重要。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，公众可以通过弗吉尼亚理工大学和西弗吉尼亚科学博物馆的剧院向公众开放。萜烯构成一大类主要为环状的分子，在生物体的化学相互作用中发挥重要作用。然而，动物体内负责萜烯环化和多样性的酶功能的出现仍然难以捉摸。研究小组将结合计算和实验方法来定义昆虫中萜烯多样性的关键酶适应——昆虫是物种最丰富的动物谱系。具体来说，该项目定义了激活异戊二烯二磷酸合酶（IDS）中萜烯环化酶（TPS）酶功能的修饰，IDS是参与核心萜烯代谢的酶。研究人员将鉴定不同昆虫类群中的萜烯环化酶并进行功能表征，以评估与昆虫中这些酶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，生成精确定位氨基酸残基网络的模型，从而触发 IDS 模板上 TPS 活动的出现。网络模型将用于构建合成酶库并帮助表征萜烯环化的突变途径。研究人员还将利用该研究的数据开发酶进化动力学的综合生物物理模型，定量描述萜烯多样性出现时酶功能的基本转变。总而言之，这个跨学科项目的见解将有助于加深对自然界酶和化学多样性重大扩展背后的生物物理原理的理解。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ancient origin and conserved gene function in terpene pheromone and defense evolution of stink bugs and hemipteran insects

萜类信息素的古老起源和保守基因功能以及椿象和半翅目昆虫的防御进化

• DOI: 10.1016/j.ibmb.2022.103879
• 发表时间: 2023
• 期刊: Insect Biochemistry and Molecular Biology
• 影响因子: 3.8
• 作者: Rebholz, Zarley;Lancaster, Jason;Larose, Hailey;Khrimian, Ashot;Luck, Katrin;Sparks, Michael E.;Gendreau, Kerry L.;Shewade, Leena;Köllner, Tobias G.;Weber, Donald C.
• 通讯作者: Weber, Donald C.