Medicinal plants produce a wealth of pharmaceutical compounds such as taxol, vincristine, and morphine. Unfortunately, the specialized secondary metabolic pathways leading to such compounds remain poorly understood and progress in elucidating and manipulating these taxonomically restricted metabolic pathways has been correspondingly slow. This has been exacerbated by the limited development of """"""""omics""""""""-level resources for medicinal plants, which has meant that as a group, research in medicinal species have not benefited to the same extent from the genomics revolution, as have research in model plants and agronomic crop species. This proposal describes the combined use of state-of-the-art sequencing technologies, metabolomics capabilities, and bioinformatics to develop an unrestricted, public resource to address this growing gap in our knowledge base of species-specific plant metabolism and accelerate the identification and functional analysis of genes involved in natural product biosynthesis in 20 widely used medicinal plant species. This resource will provide the research community with user-friendly access to the DNA sequences and expression profiles of each plant's transcriptome and associated metabolome, which we anticipate will have a translational effect on drug development. To achieve this goal, we will utilize next generation sequencing approaches to determine the near-complete set of mRNAs encoded by each medicinal plant species. Transcriptome profiling of up to 20 chemically diverse tissues/treatments per species using the RNA-Seq method from Illumina will be performed and correlated with metabolite profiles generated through LC-TOF and GC-MS for these same samples. All sequence and gene expression data will be deposited into NCBI and made available, along with metabolite profiling data at medicinalplantgenomics.msu.edu, a custom website developed by the research consortium. Thus, this NIH Grand Opportunities Grant will provide searchable and downloadable databases for medicinal plant gene sequences, expression profiles and metabolites that can be accessed and utilized by the research community to facilitate discovery of the pathways and genes responsible for biosynthesis of key pharmaceuticals. High throughput sequencing of genomes and transcriptomes has revolutionized and accelerated the pace and progress of research across the life sciences and this proposal will for the first time extend these advances into the medicinal plant arena on a broad scale.

Public Health Relevance

This proposal describes the combined use of state-of-the-art DNA sequencing technologies, metabolomics capabilities, and bioinformatics to develop an unrestricted, public resource to advance our knowledge base of species-specific plant metabolism and accelerate the identification and functional analysis of genes involved in natural product biosynthesis in 20 widely used medicinal plant species. This resource will provide the research community with user-friendly access to the DNA sequences and expression profiles of each plant's transcriptome and associated metabolome, which we anticipate will have a translational effect on drug development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
1RC2GM092521-01
Application #
7854387
Study Section
Special Emphasis Panel (ZGM1-PPBC-X (TR))
Program Officer
Jones, Warren
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$3,027,575
Indirect Cost
Name
University of Kentucky
Department
Other Basic Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Jiang, Zuodong; Kempinski, Chase; Chappell, Joe (2016) Extraction and Analysis of Terpenes/Terpenoids. Curr Protoc Plant Biol 1:345-358
Kumar, Santosh; Kempinski, Chase; Zhuang, Xun et al. (2016) Molecular Diversity of Terpene Synthases in the Liverwort Marchantia polymorpha. Plant Cell 28:2632-2650
Sadre, Radin; Magallanes-Lundback, Maria; Pradhan, Sujana et al. (2016) Metabolite Diversity in Alkaloid Biosynthesis: A Multilane (Diastereomer) Highway for Camptothecin Synthesis in Camptotheca acuminata. Plant Cell 28:1926-44
Rizhsky, Ludmila; Jin, Huanan; Shepard, Michael R et al. (2016) Integrating metabolomics and transcriptomics data to discover a biocatalyst that can generate the amine precursors for alkamide biosynthesis. Plant J 88:775-793
Rising, Kathleen A; Crenshaw, Charisse M; Koo, Hyun Jo et al. (2015) Formation of a Novel Macrocyclic Alkaloid from the Unnatural Farnesyl Diphosphate Analogue Anilinogeranyl Diphosphate by 5-Epi-Aristolochene Synthase. ACS Chem Biol 10:1729-36
Ekanayaka, E A Prabodha; Celiz, Mary Dawn; Jones, A Daniel (2015) Relative mass defect filtering of mass spectra: a path to discovery of plant specialized metabolites. Plant Physiol 167:1221-32
Bedewitz, Matthew A; Góngora-Castillo, Elsa; Uebler, Joseph B et al. (2014) A root-expressed L-phenylalanine:4-hydroxyphenylpyruvate aminotransferase is required for tropane alkaloid biosynthesis in Atropa belladonna. Plant Cell 26:3745-62
Hur, Manhoi; Campbell, Alexis Ann; Almeida-de-Macedo, Marcia et al. (2013) A global approach to analysis and interpretation of metabolic data for plant natural product discovery. Nat Prod Rep 30:565-83
Yeo, Yun-Soo; Nybo, S Eric; Chittiboyina, Amar G et al. (2013) Functional identification of valerena-1,10-diene synthase, a terpene synthase catalyzing a unique chemical cascade in the biosynthesis of biologically active sesquiterpenes in Valeriana officinalis. J Biol Chem 288:3163-73
Yamazaki, Mami; Mochida, Keiichi; Asano, Takashi et al. (2013) Coupling deep transcriptome analysis with untargeted metabolic profiling in Ophiorrhiza pumila to further the understanding of the biosynthesis of the anti-cancer alkaloid camptothecin and anthraquinones. Plant Cell Physiol 54:686-96

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