WP3: Biosynthesis as a step to bio-inspiration, from genes to molecules
The chemical diversity of natural products addressed in WP2 can be studied and manipulated at the genetic and enzymatic levels. Understanding biosynthetic pathways indeed contributes to the study of their role in nature, if knowing regulatory mechanisms, and find human applications. Investigations of the regulation, activation and repression of metabolic routes are thus essential in a systemic and integrative context as that of i-NPChem, in order to describe the subsequent chain of biological events.
Example of biosynthetically challenging compound
Today, the genetic and enzymology of biosynthetic pathways has reached an advanced stage which makes possible metabolic engineering and synthetic biology, with powerful tools for producing natural compounds of interest or metabolic analogues. For example, the production of the antimalarial drug precursor artemisinic acid, a plant compound, has been achieved through fermentation of engineered yeast.[1] The biotechnological process is now used industrially to produce this precursor whose semi-synthetic transformation into arteminisin (in a biomimetic manner) can be achieved in a few and efficient chemical steps.[2] This method of production has been capable of supplementing the world supply of artemisinin from a second source independent of the uncertainties associated with field production. The biotechnological strategy has more recently been applied to opioid.[3]
In addition, thanks to structural enzymology and computational biochemistry, it is possible to understand biosynthetic mechanisms at the atomic level. It can give clues to bio-inspired synthetic chemistry which takes inspiration from putative or proven biosynthetic pathways, to design efficient strategies of chemical production as described in WP4.[4]
[1] D.-K. Ro, E. M. Paradise, M. Ouellet et al. Nature2006, 440, 940-943.
[2] C. J. Paddon, P. J. Westfall, D. J. Pitera et al. Nature2013, 496, 528-532.
[3] M. Höhne and J. Kabisch, Angew. Chem. Int. Ed. 2016, 55(4), 1248–1250.
[4] E. Poupon and B. Nay (Eds) Biomimetic Organic Synthesis (2011), Wiley-VCH: Weinheim.
been achieved through fermentation of engineered yeast.[1] The biotechnological process is now used industrially to produce this precursor whose semi-synthetic transformation into arteminisin (in a biomimetic manner) can be achieved in a few and efficient chemical steps.[2] This method of production has been capable of supplementing the world supply of artemisinin from a second source independent of the uncertainties associated with field production. The biotechnological strategy has more recently been applied to opioid.[3]
an IRN on Integrative Natural Product Chemistry 