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.

生物之间的化学相互作用代表了自然界的一种关键交流形式，并由各种小分子介导。 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至关重要的作用。研究人员使用跨学科的方法探讨了如何出现化学化合物的问题，并采用生物学功能，侧重于理解萜烯的出现 - 昆虫用来阻止敌人和病原体，寻找食物，寻找食物并吸引或吸引或吸引对象的主要分子家族。该项目整合了计算建模和分子修饰，重建了昆虫中萜烯化学多样性至关重要的酶的演变。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，该平台将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，包括潜在的目标酶产品和用于工业应用的基因变体，以及将研究结果转化为视觉装置，这将通过弗吉尼亚理工大学和西弗吉尼亚州科学博物馆的剧院访问。萜烯构成了一大批循环分子，在生物体的化学相互作用中具有主要作用。然而，导致动物萜烯的环化和多样性的酶促功能的出现仍然难以捉摸。研究团队将采用计算方法和实验方法的组合来定义昆虫中萜烯多样性的关键酶促适应，这是动物种类繁多的谱系。具体而言，该项目定义了激活异源二磷酸合酶（IDS）中萜烯环酶（TPS）酶促功能的修饰，该酶是参与核心萜烯代谢的酶。研究人员将在各种昆虫分类单元中识别并在功能上表征萜烯环化酶，以评估与昆虫中这些酶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，以生成模型来查明氨基酸残基网络，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，并有助于表征构成萜烯环化的突变途径。研究者还将使用研究中的数据来开发酶进化动力学的综合生物物理模型，这些模型在萜烯多样性的出现中定量地描述了酶功能的基本过渡。累积地，这个跨学科项目的见解将导致对自然界中酶促和化学多样性的重大扩展背后的生物物理原理的了解。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准来通过评估来支持的。

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.

Terpene synthases and pathways in animals: enzymology and structural evolution in the biosynthesis of volatile infochemicals

• DOI: 10.1039/d2np00076h
• 发表时间: 2023-03-07
• 期刊: NATURAL PRODUCT REPORTS
• 影响因子: 11.9
• 作者: Tholl，Dorothea;Rebholz，Zarley;O'Maille，Paul E.
• 通讯作者: O'Maille，Paul E.