Beskrivelse
Photosynthetic organisms are able to use solar energy and carbon dioxide for the production of organic compounds. Based on initial formation and subsequent turn-over of carbohydrates, plants channel energy flux and carbon into specific biosynthetic pathways to optimize growth and development and adapt to environmental challenges by producing bioactive defense compounds when attacked by insects and microbes. Several of these bioactive defense compounds are structurally complex and highly valuable pharmaceuticals used in the treatment of serious human diseases like cancer. Unfortunately such bioactive natural products are typically produced in small amounts by plants. Most of the pathways responsible for the formation of the compounds involve cytochrome P450 catalyzed key steps difficult to copy using organic chemical synthesis. Using the “share-your- parts” principle of synthetic biology, we have now succeeded in breaking the evolutionary compartmentalization of energy generation and production of bioactive natural products by relocating an entire P450-dependent pathway for a bioactive natural product into to the chloroplast and driving the pathway by direct use of the reducing power generated by photosystem I in a light-dependent manner. The enzymes catalysing the pathway were targeted to the chloroplast by being expressed as fusion proteins with the transit peptide sequence from ferredoxin. The long term goal is to build a supra-molecular enzyme complex catalysing light driven synthesis of pharmaceuticals and other interesting bioactive molecules. The production systems are being developed and optimised using transient expression in tobacco as the experimental system followed by stable transformation of cyanobacteria and moss strains grown in closed photobioreactors. Key target compounds are structurally complex diterpenoids that are costly to synthesise by chemical means such as forskolin and ingenol-3-angelate. Our progress in identifying the genes involved in the latter pathways will be presented in the lecture .Periode | 20 okt. 2014 |
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Begivenhedstitel | Rothamsted Research |
Begivenhedstype | Konference |
Placering | London, StorbritannienVis på kort |