TERPMED

Plant Terpenoids for Human Health: a chemical and genomic approach to identify and produce bioactive compounds

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 Obiettivo del progetto (Objective)

'Plant secondary metabolites are an important source of therapeutic drugs or drug leads. The advent of genomic and metabolomic technologies has now made it possible to bring the field of plant natural products into the 21st century and replace serendipitous and haphazard finding by rational design and discovery. This proposal is devoted to plant terpenes, the largest and most diverse group of plant natural products. TERPMED will focus on sesquiterpene lactones and phenolic diterpenes because of the presence of distinct functional groups and their high potential as novel human drugs for treating cancer and neurological disorders. By using a combination of comparative metabolomics and genomics, significant advances will be achieved in the understanding of the biosynthetic pathways of these compounds. Focusing on specific functional groups such as γ-butyrolactones and phenolics amongst the terpenes will allow the development of high-throughput analytical methodologies to detect, purify and characterize compounds bearing these groups. A comprehensive library of these compounds within a subset of plant biodiversity will be established. The compounds isolated will be tested for biological activity and the most active molecules will be selected. High throughput cDNA sequencing coupled to the comparative analysis of the metabolic profiles of targeted species will be achieved for the elucidation of the biosynthetic pathways of these compounds. Innovative production platforms using plant secretory organs such as the trichomes will be tested for the pilot production of the most promising compounds identified and the production of novel compounds by combinatorial biosynthesis.'

Descrizione progetto (Article)

Look on any uncultivated hillside and you are likely to find medicinal plants. In particular, feverfew (Tanacetum parthenium) and rosemary (Rosmarinus officinalis) can both be found growing wild in southern Europe, and feverfew, with its cold tolerance, is indigenous throughout northern Europe.

Both feverfew and rosemary produce chemicals of the terpenoid class that are well known for a variety of health-promoting properties such as their anti-bacterial, anti-inflammatory, neuroprotective and anti-cancer abilities. The European-backed TERPMED project focuses on two types of terpenoids that can be isolated from feverfew and rosemary: sesquiterpene lactones (SLs) and phenolic diterpenes (PDs).

TERPMED scientists developed analytical tools that targeted SLs and PDs, as well as hundreds of other metabolites in order to establish the chemical diversity of these medicinal plant species. The SL and PD compounds were subsequently tested for biological activity. After determining where the molecules of interest were predominantly produced and stored in the plants, sequencing data was generated from ribonucleic acid (RNA) to pinpoint the genes and enzymes responsible for their production.

The genes are used to reconstruct the biosynthetic pathways of the bioactive compounds in other plant systems, which will become pilot-scale green factories. The genetic sequences are also being used to generate new functional molecules using combinatorial biosynthesis approaches. All information about genes, enzymes and the hundreds of compounds isolated from the plants is stored in the project database, which is continuously updated with new data generated in the project and is available through the project website (http://www.terpmed.eu).

TERPMED achievements stand to be able to supply the pharmaceutical industry with new drugs to treat many diseases including central nervous system disorders and cancer.