Building a Highly Automated Metabolic Pathway Reconstruction Infrastructure for Plants

Pi：Seung Yon(Sue)Rhee(卡内基科学研究所)主要合作者：Peter Karp(SRI国际)对植物的基本了解进行创新，并在该领域有效地应用这些知识，对于应对21世纪的能源和食品安全挑战至关重要。测序技术的快速发展将使已测序的植物基因组数量成倍增加。为了促进酶的发现、基于代谢特性的育种和代谢工程，人们越来越需要将测序的基因组置于生化环境中。满足不断增长的对食品、生物燃料和植物制药生产的需求，将需要全面和准确地了解控制植物新陈代谢的酶、途径和调控网络。该项目将开发一条自动化管道，根据基因组规模的序列和功能基因组数据重建高质量的植物代谢途径。这条管道将用于为18种在农业和工业上具有重要意义的植物创建可自由访问的代谢途径数据库。这些特定物种数据库和多物种PlantCyc参考数据库将通过以文献为基础的酶和途径管理增加更多的价值。此外，新的实验支持的途径调节和代谢流量数据将被添加到这些数据库中，以指导合理的代谢工程。计算管道、参考和特定物种的数据库以及特定植物的限速酶反应和转录调控关系集将有助于系统地描述植物新陈代谢和代谢工程的特征。该项目产生的资源的能见度、效用和潜在影响将通过在路径验证和管理过程中聘请研究具有商业价值和社会价值的“孤儿作物”的专家科学家来提高。全世界有超过7000名研究人员承诺参与重建他们感兴趣的物种的途径数据库。该项目还将培训当地社区大学的几名本科生实习生，以创建有价值的物种标记植物化合物数据资源。实习生将增加他们的生物学知识，熟悉大量有价值的在线资源。此外，他们接触卡内基研究所的科学家可能会促使他们从事生物研究事业。该项目还计划激发人们对植物新陈代谢的热情，特别是在代表不足的高中生群体中。该项目将与一所公立特许学校的一名高中教师合作，制作一个关于植物新陈代谢的教学模块，与州和国家生物教育标准相联系。它将在几所为代表不足的少数族裔和低收入学生提供服务的学校展出。它还将在项目网站上免费提供，并积极向高中生物教师传播。该项目产生的所有数据、工具和教材将从项目网站(http://plantcyc.org)，)公开和免费获取，方法是在知识共享“类似共享”许可证(http://creativecommons.org/licenses/bysa/3.0/)，下下载完整的数据库，并将大量数据集作为可下载的文本文件。

PI: Seung Yon (Sue) Rhee (Carnegie Institution for Science)Key Collaborator: Peter Karp (SRI International)Innovations in the basic understanding of plants and effective application of that knowledge in the field are essential to meet energy and food security challenges in the 21st century. Rapid advances in sequencing technologies will increase the number of sequenced plant genomes exponentially. There is a growing need to place the sequenced genomes in a biochemical context in order to facilitate enzyme discovery, metabolic-trait based breeding and metabolic engineering. Meeting the ever-expanding demand for food, biofuel and phytopharmaceutical production will require a comprehensive and accurate understanding of the enzymes, pathways and regulatory networks that control metabolism in plants. This project will develop an automated pipeline to reconstruct high-quality plant metabolic pathways from genome-scale sequence and functional genomics data. This pipeline will be used to create freely accessible metabolic pathway databases for 18 agriculturally and industrially important plants. Further value will be added to these species-specific databases and the multi-species PlantCyc reference database through literature-based curation of enzymes and pathways. In addition, new experimentally supported pathway regulation and metabolic flux data will be added to these databases to guide rational metabolic engineering. The computational pipelines, reference and species-specific databases and plant-specific "gold-standard" sets of rate-limiting enzymatic reactions and transcriptional regulatory relationships will facilitate systematic characterization of plant metabolism and metabolic engineering. The visibility, utility and potential impact of the resources generated by this project will be increased by engaging expert scientists working on both commercially valuable and socially valuable "orphan crops" in the pathway validation and curation process. Over 7 researchers world-wide have committed to participating in reconstructing pathway databases for their species of interest. The project will also train several undergraduate interns from a local community college to create a valuable species-tagged plant compound data resource. The interns will increase their biological knowledge and familiarity with a large number of valuable on-line resources. Furthermore, their exposure to scientists at the Carnegie Institution may prompt them to pursue a career in biological research. The project also plans to stimulate enthusiasm for plant metabolism, especially among under-represented groups of high school students. The project will collaborate with a high school teacher at a public charter school to produce a teaching module on plant metabolism that connects to state and national biology education standards. It will be presented at several schools serving under-represented minority and low-income students. It will also be made freely available at the project website and actively disseminated to high school biology teachers. All the data, tools and teaching materials produced from this project will be publicly and freely accessible from the project website (http://plantcyc.org), through complete database downloads under a Creative Commons "share-alike" license (http://creativecommons.org/licenses/bysa/3.0/), and as bulk data sets as downloadable text files.