Collaborative Proposal: Biosynthesis of Alkamides - Experimental Modeling of a Modular Secondary Metabolic Pathway

合作提案：烷酰胺的生物合成 - 模块化次级代谢途径的实验模型

• 批准号: 0919743
• 负责人: Basil Nikolau
• 金额: $ 43.55万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0919743&HistoricalAwards=false
• 关键词: Collaborative; Proposal; Biosynthesis; Alkamides; Experimental

Intellectual Merit: Alkamides (amides linked to fatty acids) are novel plant secondary compounds that are poorly characterized, but that accumulate to significant levels in Echinacea, making this plant of choice to study these compounds and their biosynthesis. Our understanding of alkamide function in plants is in its infancy, but recent data suggest these compounds may have novel signaling functions in addition to insecticidal properties. This work will lay the foundation for further studies of the importance of these compounds in plant biology as well as open up research on this plant genus which has been used medicinally for hundreds of years. Because the pathways in alkamide biosynthesis involve amino acid metabolism and novel chemical linkages, there are also multiple future biotechnological applications for the enzymes involved. The proposed research will strategically apply high-throughput global profiling technologies to elucidate this natural product biosynthetic pathway. Alkamides appear to be biologically assembled via a modular metabolic pathway that may be an adaptation of amino acid and fatty acid metabolism. Experiments that combine metabolite profiling, metabolic flux studies and transcriptomics will be used to identify genes and enzymes that assemble a diverse collage of alkamides. Defining the alkamide pathway offers the potential of discovering new metabolic processes that generate novel combinations of chemical functionalities, which have wide-ranging applications (e.g., lubrication and detergent industries). In addition, this research project outlines a general methodology that should be broadly applicable to discovering how primary and specialized plant metabolism are juxtaposed and evolve to generate the physiochemical phenotypic differences among plant taxonomic groups. The multilayered bio-prospecting to be used offers the opportunity to browse the metabolic repertoire of an organism, and the system-wide knowledge of the involved biochemical processes should translate to the creation of novel bio-derived compounds relevant to the chemical industries, as well as strategies for pest resistance.Broader Impacts: This project will facilitate a multidisciplinary partnership between IUPUI, ISU researchers and scientists at the USDA North Central Regional Plant Introduction Station. The collaboration established to conduct this research will mentor young scientists at the increasingly uncommon intersection of organic chemistry, mechanistic biochemistry and functional genomics through the coeducation of undergraduates, graduate students and post-doctoral fellows. Students at IUPUI, a large, urban university, will be drawn from a trainee pool rich in underrepresented minority and first generation students in the McNair and Diversity Scholars STEM research programs. These interactions will allow the project to operate synergistically with IUPUI campus initiatives to mentor undergraduate students toward graduate education. As an outreach activity specific to IUPUI, high school teachers will experience hands-on research. In conjunction with the graduate students, they will engage in experiments leading to biochemical lessons suitable for use at their home schools. This effort dovetails with ongoing NSF GK-12 participation in IUPUI's research programs. At ISU, undergraduates will translate the proposed research into a module in a new course in biotechnological biochemistry.

智力优点：烷酰胺（与脂肪酸相关的酰胺）是新型植物的次要化合物，其特征较差，但在紫锥菊中积累至显着水平，使这种选择这些化合物及其生物合成的植物使得这种植物。我们对植物中烷酰胺功能的理解仍处于起步阶段，但最近的数据表明，除了杀虫特性外，这些化合物还具有新颖的信号传导功能。这项工作将为进一步研究这些化合物在植物生物学中的重要性以及对该植物属的研究开放，该研究已被药物使用了数百年。由于烷酰胺生物合成的途径涉及氨基酸代谢和新颖的化学联系，因此对所涉及的酶也有多种将来的生物技术应用。拟议的研究将在战略上采用高通量全球分析技术来阐明这种天然产物生物合成途径。 烷酰胺似乎是通过模块化代谢途径在生物学上组装的，该途径可能是氨基酸和脂肪酸代谢的适应性。 结合了代谢产物分析，代谢通量研究和转录组学的实验将用于鉴定聚集烷酰胺拼贴的基因和酶。 定义烷酰胺途径的潜力是发现新的代谢过程，从而产生具有广泛应用的化学功能组合的新型组合（例如，润滑和洗涤剂行业）。 此外，该研究项目概述了一种通用方法，该方法应该广泛地适用于发现主要和专业的植物代谢是如何并置并演变以在植物分类群中产生生理化学表型差异。 使用的多层生物培训为浏览有机体的代谢曲目提供了机会，并且对所涉及的生物化学过程的全系统知识也应转化为与化学工业相关的新型生物衍生化合物的创造，以及作为害虫抗性的策略。BRODER的影响：该项目将促进IUPUI，ISU研究人员和科学家之间的多学科合作伙伴关系。为进行这项研究而建立的合作将指导年轻科学家通过在本科生，研究生和博士后研究员的同意中越来越不常见的有机化学，机械生物化学和功能基因组学交集。 IUPUI的学生是一所大型城市大学，将从富含代表性不足的少数民族和第一代学生的学员和多元化学者STEM研究计划中的第一代学生中汲取灵感。这些互动将使该项目能够与IUPUI校园倡议协同运作，以指导本科生到研究生教育。作为特定于IUPUI的外展活动，高中老师将体验动手研究。与研究生一起，他们将进行实验，从而导致适合在其家庭学校使用的生化课程。这项工作与正在进行的NSF GK-12参与IUPUI的研究计划相吻合。在ISU，本科生将在生物技术生物化学的新课程中将提议的研究转化为一个模块。