Scientists receive $3 million from NIH to uncover how plants make medicinal compounds

Researchers use $3 million to analyze synthesis of medicinal chemicals

Scientists at Michigan State University are receiving nearly $3 million from the National Institutes of Health to uncover how several popular plants make medicinal compounds.

The funding, part of a larger $6 million award via the American Recovery and Reinvestment Act, will provide scientists the resources to understand exactly which genes are involved in the synthesis of medicinal chemicals in several plants -- clearing the way for cheaper and more effective ways to produce drugs.

"Many plants make compounds that we use directly as medicines or that we modify slightly to create widely used medicines, but in almost all cases we do not understand how the plants synthesize these compounds," said MSU biochemistry professor Dean DellaPenna, one of three principle investigators on the grant. "Identifying and understanding the genes involved in the synthesis of these plant compounds is a first step that can lead to new drug development and increased production efficiency."

Scientists on the grant -- including researchers at the University of Kentucky and the Massachusetts Institute of Technology -- are using three key techniques:

• Transcriptomics allows scientists to learn which of the roughly 30,000 genes in a plant are actively being transcribed into RNA in a tissue and the exact expression level of each gene.

• Metabolomics allows assessment of the types and levels of several hundred chemicals within the tissue (some of which are medicinal compounds, some of which are biosynthetic precursors).
• Bioinformatics then combines these two very large data sets to figure out which genes are being expressed in concert with specific chemicals and thereby provide scientists with a short list of those genes most likely to be involved in synthesis of the medicinal compound of interest.

The research team then will conduct additional research to demonstrate each of these gene's individual functions in detail and provide the basis for synthetic biology techniques needed to develop drugs.

"Plants are better chemists than people, so understanding the biosynthesis and exactly how plants are able to do this provides a powerful base of knowledge for improving medicine and health," said Dave Dewitt, associate dean for research in the College of Natural Science. "Seeing the genome of a plant is like looking at a list of 30,000 parts without the instruction manual of how it all comes together to work."

The research relies on high-throughput DNA sequencers at MSU. Each experiment can yield as many as 500 million base pairs of DNA sequence, and the entire project will generate approximately 240 billion base pairs of information, the equivalent of roughly 80 human genomes.

"Ongoing advancements in life sciences technology allows us to efficiently interrogate these very large parts lists and efficiently do experiments on a scale that just wasn't possible three years ago," Dewitt said. "DNA sequencing and metabolite analysis has become immensely more efficient to a point where we can make new discoveries using methods and approaches previously not easily employed in metabolic engineering."

The 14 plants the scientists will be researching include Digitalis purpurea (foxglove), from which the heart drug digitoxin is derived; Atropa belladonna, from which the drug Atropine is produced; and Catharanthus roseus (periwinkle), from which the anti-cancer drugs vincristine and vinblastine are obtained.