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Light-driven Chemical Synthesis using Cytochrome P450s

Final Report Summary - LIGHTDRIVENP450S (Light-driven Chemical Synthesis using Cytochrome P450s)

In this research initiative, we have established solar light driven production of high value diterpenoids using tobacco, algae, cyanobacteria and yeast as production hosts. Focus has been on the two diterpenoids forskolin and ingenol-3-angelate. The photosynthetic systems do not yet provide nearly as high yields as may be obtained in yeast but are highly promising as they are environmentally benign affording production of high value products using carbon dioxide from the air as the sole carbon source and sunlight as a renewable energy source to drive the reactions. The research has shown that entire pathways for high value natural products may be transferred to the thylakoid membranes of the photosynthetic hosts. By introduction of optimal electron carrier proteins, solar light driven electron transfer from photosystem I has been channeled directly to the cytochrome P450s. Furthermore, the extremely important discovery of the impact of specific isoforms of cytochrome b5 in upscaling of compound production lead us to expect specific cytochrome b5 isoforms to become a defining factor of large-scale diterpenoids production. The envisioned commercial production system to be developed for production of forskolin and ingenol-3-angelate can easily be adapted to production of a multitude of other high value compounds. The development of this type of production systems will facilitate the transfer to a biobased society.