Transcriptome Characterization of Medicinal Plants Relevant to Human Health

与人类健康相关的药用植物的转录组表征

基本信息

批准号：
7943054
负责人：
RODNEY B CROTEAU
金额：
$ 129.06万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7943054
关键词：
Anabolism Animal Model Area Biochemical Biochemical Pathway Biochemistry Bioinformatics Biological Factors Biological Process Carbon Cell Culture Techniques Cells Chicago Classification Clinical Trials Code Communities Complex Computer software DNA Sequence Data Databases Deposition Development Engineering Enzymatic Biochemistry Enzyme Gene Enzymes Evaluation Foundations Gene Expression Profile Genes Genetic Genetic Transcription Genomics Goals Harvest Health Homologous Gene Housing Human Illinois Imagery Investigation Knowledge Lead Life Medicinal Plants Metabolic Metadata Modification Molecular Biology Molecular Genetics Molecular Profiling Museums Online Systems Orphan Outcome Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Phytochemical Plant Sources Plants Process Production Public Health RNA Sequences Reaction Regulation Regulator Genes Reporting Research Research Infrastructure Research Personnel Resources Seasons Source Specificity Specimen Staging Structure Study models Technology Time Tissues Transcript Universities Validation Variant Work abstracting base cell type chemical synthesis comparative cost directed evolution drug development enzyme pathway gene discovery genetic variant genome wide association study improved novel public health relevance success synthetic biology tool transcription factor user-friendly voucher web-accessible

项目摘要

DESCRIPTION (provided by applicant): Plants are the source of many important medicinal compounds and the diversity of plant species and biochemistry suggests that many more are potentially available. The current understanding of the formation of plant-derived medicinal compounds at the enzyme, gene and regulatory levels is very incomplete-not a single complex plant medicinal pathway has yet to be completely elucidated at both the enzyme and the regulatory level. Historically, most studies of plant-derived medicinal compounds have been very narrowly focused, typically devoted to very specific steps in a particular biosynthetic pathway. These investigations were often pioneering-the diversity of plant biochemistry contains many novel reactions-but they were also very labor- intensive. More recently, genome-wide studies of model plant species have resulted in an explosive increase in our knowledge of, and capacity to understand, basic biological processes. Working from the genetics to the biochemistry now provides the most efficient way to build a long awaited and urgently needed foundation for more effectively probing and exploiting plant medicinal compound biosynthetic pathways. Having a comprehensive medicinal plant transcriptome database would propel medicinal plant species from an orphan- like status into the limelight of plant biochemistry and molecular genetics. The long-term goal of this research is for the scientific community to understand the complete formation, storage and regulation of plant-derived medicinal compounds at the enzyme and gene level. Improved understanding will enable the development of alternate sources of known pharmaceuticals and of novel drugs. The objective of this proposal is to provide the research community with urgently needed infrastructure and resources to enable comprehensive studies of the most compelling and medicinally significant plant biosynthetic pathways. Its Specific Aims are 1) To validate carefully selected medicinal plants based on taxonomic classification, medicinal compound accumulation and target transcript analysis, 2) To conduct transcriptome profiling of these medicinal plants and 3) To disseminate the accumulated data to the scientific community in the form of a user-friendly database. The resultant database and tools for comparative analysis will lead to gene discovery and enable technologies in the broader medicinal plant field. It is expected that the entire field of plant-derived pharmaceuticals will be advanced to a higher, more comprehensive level of analysis as a result of the proposed research. This is significant because the results will provide researchers in the field of plant-derived pharmaceuticals with a publicly available database and search tools for comparative analyses of pathway enzyme-coding genes and regulatory factors. These tools will enable gene discovery, metabolic engineering, synthetic biology and directed evolution for the improved production of drugs and for the development of novel drugs. Taken together, we envisage that this will ultimately result in tangible long-term and meaningful benefits for public health. PUBLIC HEALTH RELEVANCE: This research is directed toward understanding the various regulatory and biochemical factors that control medicinal compound formation, transport and storage in medicinal plants. Success in this area offers the promise of providing less expensive and/or novel medicinals that could positively impact the lives of hundreds of millions of people.

描述（由申请人提供）：植物是许多重要药用化合物的来源，植物物种和生物化学的多样性表明还有更多的潜在可用化合物。目前对植物源药用化合物在酶、基因和调控水平上的形成的理解非常不完整——在酶和调控水平上还没有一个单一的复杂植物药用途径尚未被完全阐明。从历史上看，大多数对植物源性药用化合物的研究都非常集中，通常致力于特定生物合成途径中的非常具体的步骤。这些研究往往是开创性的——植物生物化学的多样性包含许多新颖的反应——但它们也非常耗费人力。最近，对模式植物物种的全基因组研究使我们对基本生物过程的了解和理解能力得到了爆炸性的增长。从遗传学到生物化学的研究现在提供了最有效的方法来建立期待已久且迫切需要的基础，以便更有效地探索和开发植物药用化合物的生物合成途径。拥有一个全面的药用植物转录组数据库将推动药用植物物种从孤儿状态进入植物生物化学和分子遗传学的聚光灯下。这项研究的长期目标是让科学界在酶和基因水平上了解植物源药用化合物的完整形成、储存和调控。加深了解将有助于开发已知药物和新药物的替代来源。该提案的目的是为研究界提供迫切需要的基础设施和资源，以便能够对最引人注目和具有药用意义的植物生物合成途径进行全面研究。其具体目标是 1) 根据分类学分类、药用化合物积累和目标转录物分析来验证精心挑选的药用植物，2) 对这些药用植物进行转录组分析，3) 以以下形式向科学界传播积累的数据一个用户友好的数据库。由此产生的数据库和比较分析工具将导致基因发现并在更广泛的药用植物领域实现技术。由于拟议的研究，预计整个植物源药物领域将提升到更高、更全面的分析水平。这很重要，因为研究结果将为植物源药物领域的研究人员提供一个公开的数据库和搜索工具，用于途径酶编码基因和调控因子的比较分析。这些工具将使基因发现、代谢工程、合成生物学和定向进化成为可能，从而改善药物生产和开发新药物。总而言之，我们预计这最终将为公众健康带来切实、长期且有意义的利益。公共健康相关性：本研究旨在了解控制药用植物中药用化合物形成、运输和储存的各种调节和生化因素。这一领域的成功有望提供更便宜和/或新颖的药物，从而对数亿人的生活产生积极影响。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Next generation sequencing in predicting gene function in podophyllotoxin biosynthesis.

下一代测序预测鬼臼毒素生物合成中的基因功能。

DOI：
发表时间：
2013-01-04
期刊：
影响因子：
0
作者：
Marques, Joaquim V;Kim, Kye;Lee, Choonseok;Costa, Michael A;May, Gregory D;Crow, John A;Davin, Laurence B;Lewis, Norman G
通讯作者：
Lewis, Norman G

The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery.

石蒜科生物碱：生物合成和酶发现方法。

DOI：
发表时间：
2016-06
期刊：
影响因子：
0
作者：
Kilgore, Matthew B;Kutchan, Toni M
通讯作者：
Kutchan, Toni M

Accurate mass-time tag library for LC/MS-based metabolite profiling of medicinal plants.

用于基于 LC/MS 的药用植物代谢物分析的准确质量时间标签库。

DOI：
10.1016/j.phytochem.2013.02.018
发表时间：
2013-07
期刊：
Phytochemistry
影响因子：
3.8
作者：
Cuthbertson DJ;Johnson SR;Piljac-Žegarac J;Kappel J;Schäfer S;Wüst M;Ketchum RE;Croteau RB;Marques JV;Davin LB;Lewis NG;Rolf M;Kutchan TM;Soejarto DD;Lange BM
通讯作者：
Lange BM

Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities.

具有石蒜科生物碱生物合成相关活性的去甲氧马利替丁还原酶的鉴定。