Objective
The goal of this proposed research initiative is to engineer chloroplasts into production units for high value bio-active natural products. The first aim is to re-route the biosynthetic pathways for these compounds into the chloroplast and to boost compound formation by optimizing and channeling reducing power from photosystem I into to the energy demanding steps. By these measures we aim to overcome the inherent limitations in plants to channel photosynthetic fixed carbon and reducing power directly into production of desired bioactive natural products. Our production targets are diterpenoids with the anti-cancer drug ingenol-3-angelate and the adenylyl cyclase activator forskolin as the two chosen test compounds. Formation of the complicated hydroxylated core structures of these compounds is catalyzed by diterpenoid synthases and cytochrome P450s. These will be identified and expressed in the chloroplast. The ultimate aim is to construct a single supramolecular enzyme complex effectively using solar energy to produce complex diterpenoids. This will be accomplished by tethering the terpenoid synthases and the key P450 enzymes directly to the photosystem I complex using some of the small membrane spanning subunits of photosystem I as membrane anchors. The experimental systems used will initially be transient expression in tobacco and then move to stably transformed moss (Physcomitrella patens). The production system is built on the “share your parts” principle of synthetic biology and the aim is to construct a modular ‘tool box’ as template for tailoring the synthesis of a whole range of valuable bioactive diterpenoids. Typically, these are difficult to obtain because they are produced in very low amounts in plants difficult to cultivate. The proposal opens up entirely new research horizons and removes current bottlenecks in industrial exploitation. The technology holds the promise of true sustainability as it is driven by solar power and CO2.
Fields of science
Call for proposal
ERC-2012-ADG_20120314
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Funding Scheme
ERC-AG - ERC Advanced GrantHost institution
1165 Kobenhavn
Denmark