Transcriptome Characterization of Medicinal Plants Relevant to Human Health

描述(申请人提供)：植物是许多重要的药用化合物的来源，植物物种和生物化学的多样性表明有更多的潜在可用。目前在酶、基因和调控水平上对植物源性药物形成的了解还很不完整--还没有一个单一的复杂的植物药物途径在酶和调控水平上被完全阐明。从历史上看，大多数对植物来源的药物化合物的研究都是非常狭隘的，通常致力于特定生物合成途径中非常具体的步骤。这些研究往往是开创性的--植物生物化学的多样性包含了许多新的反应--但它们也非常劳动密集型。最近，对模式植物物种的全基因组研究导致了我们对基本生物学过程的了解和理解能力的爆炸性增长。现在，从遗传学到生物化学的工作为更有效地探索和开发植物药物化合物的生物合成途径提供了最有效的途径，为建立期待已久和迫切需要的基础奠定了基础。拥有一个完整的药用植物转录组数据库将把药用植物物种从孤儿状态推向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来源药物化合物的完整形成、储存和调节。提高认识将有助于开发已知药物和新药的替代来源。这项提议的目的是为研究界提供迫切需要的基础设施和资源，使其能够对最引人注目和最具医学意义的植物生物合成途径进行全面研究。它的具体目标是1)根据分类、药物化合物积累和目标转录本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)以用户友好的数据库的形式向科学界传播积累的数据。由此产生的数据库和比较分析工具将导致基因发现，并使更广泛的药用植物领域的技术成为可能。预计由于拟议的研究，植物衍生药物的整个领域将提高到更高、更全面的分析水平。这一结果意义重大，因为这些结果将为植物衍生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，用于对途径、酶编码基因和调节因子进行比较分析。这些工具将促进基因发现、代谢工程、合成生物学和定向进化，以改进药物生产和开发新药。综上所述，我们预计这最终将为公共卫生带来切实、长期和有意义的好处。 公共卫生相关性：这项研究旨在了解控制药用植物中药物化合物的形成、运输和储存的各种调节和生化因素。这一领域的成功提供了提供更便宜和/或新颖的药物的希望，这些药物可能会对数亿人的生活产生积极影响。

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.