Transcriptome Characterization of Medicinal Plants Relevant to Human Health

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，有更多的潜在可用性。目前对植物源性药物化合物在酶、基因和调控水平上形成的认识非常不完整，没有一条复杂的植物药物途径在酶和调控水平上都得到了完全的阐明。从历史上看，大多数植物源性药物化合物的研究都非常狭隘，通常致力于特定生物合成途径中的非常具体的步骤。这些研究通常是开创性的——植物生物化学的多样性包含许多新颖的反应——但它们也非常耗费劳动。最近，模式植物物种的全基因组研究导致了我们对基本生物过程的知识和理解能力的爆炸性增长。从遗传学到生物化学的工作现在提供了最有效的方法，为更有效地探测和开发植物药用化合物的生物合成途径建立了一个期待已久和迫切需要的基础。建立一个全面的药用植物转录组数据库，将推动药用植物从一个孤儿的状态进入植物生物化学和分子遗传学的聚光灯下。本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性药用化合物的完整形成、储存和调控。增进了解将有助于开发已知药物和新药的替代来源。本提案的目的是为研究界提供急需的基础设施和资源，以便对最引人注目和具有医学意义的植物生物合成途径进行全面研究。其具体目标是：1)通过分类、药用化合物积累和靶转录物分析对精心挑选的药用植物进行验证；2)对这些药用植物进行转录组分析；3)将积累的数据以用户友好型数据库的形式向科学界传播。由此产生的数据库和比较分析工具将导致更广泛的药用植物领域的基因发现和启用技术。预计整个植物源性药物领域将被推进到一个更高、更全面的分析水平，作为拟议研究的结果。这是非常重要的，因为该结果将为植物源性药物领域的研究人员提供一个公开可用的数据库和搜索工具，用于途径酶编码基因和调节因子的比较分析。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，以改善药物生产和开发新药。总之，我们设想这将最终为公共卫生带来切实的长期和有意义的利益。

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.