To carry out their activities, Research Teams of the Frédéric Joliot Institute for Life Sciences have developed high-profile technological platforms in many areas : biomedical imaging, structural biology, metabolomics, High-Throughput screening, level 3 microbiological safety laboratory...
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Scientific result | Biotechnology | Structural biology
Muriel Gondry's Research Team (I2BC @ Saclay / SBIGeM), in collaboration with SIMOPRO and Biomolecules Laboratory of the Sorbonne University's one, produced 200 cyclodipeptides containing non-natural amino acids by luring and diverting the cellular machinery for the synthesis of proteins. This unprecedented approach significantly increases the diversity of these bioactive molecules.
The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates. We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5-DKPs. Such diversity could be further expanded, for example, by using various cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways.Read the French version.
Canu N, Belin P, Thai R, Correia I, Lequin O, Seguin J, Moutiez M, Gondry M Non-canonical Amino Acid Incorporation into 2,5-Diketopiperazines by Cyclodipeptide Synthases. (2018) Angew. Chem., sous pressehttp://dx.doi.org/10.1002/ange.201712536
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