Obiettivo
Coleus forskholii is a shrub of the Lamiaceae family, used as an ayurverdic medicinal plant. The roots of this plant are producing a labdane type diterpene named forskolin, known mainly for its pharmaceutical activity for protection against heart failure problems, hypertension treatment as it acts as vasodilator, anti-inflammatory properties and its effects in treating respiratory track problems. The medicinal activities of forskolin are due to its ability to activate the enzyme adenylyl cyclase and therefore to increase the levels of cyclic AMP (cAMP) in the cells. Today it is known that forskolin is produced exclusively by the roots of the species Coleus forskohlii, together with a plethora of different diterpenes, hence its availability is restricted. Thus, the aim of this research proposal is to set the base for the elucidation of the coleus diterpenoids pathways and second to generate production platforms for the controlled biotechnological synthesis of the metabolites of interest. This will be achieved using state of the art technologies and methodologies. New generation sequencing will be used for deep sequencing of the root bark transcriptome (the specialized root tissue responsible for the synthesis and accumulation of forskolin). Genes involved in forskolin and other diterpenoids production will be identified from the generated data bases, will be cloned and functionally characterized for identifying their exact role in the pathways. Upon characterization, selected genes will be expressed in the microbe yeast and/or in the moss Physcomitrella (a novel plant based terpenoid production platform, exhibiting numerous advantages in comparison with microbial systems) for the sustainable production of pure bioactive diterpenoids, which will enable the studies of the therapeutical properties of these metabolites but also the future scalable-up applications to meet pharmaceutical/commercial interests.
Campo scientifico
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2012-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
1165 Kobenhavn
Danimarca