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Technology & Strategy
Classical strategy in Natural Products-based Drug Discovery begins with the isolation of environmental samples, extract analysis, dereplication, lead identification and, finally, optimization and the choice of a candidate for development. EntreChem strategy for putting Natural Products back in the forefront of Drug Discovery avoids the early stages of the classical approach and starts with a known lead compound (an approved, clinical stage or bioactive described molecule) over which we apply our technology to obtain NCEs out of reach by other methods. These NCEs could provide a better candidate for preclinical development.
Since we obtain analogs of products with known properties, we are reducing technical and commercial risks associated to previously unknown product families.

Recent developments in recombinant DNA technology have enabled rapid advances in the cloning of gene clusters involved in the biosynthesis of many bioactive Natural Products produced by microorganisms, as well as detailed knowledge of their metabolic pathways, significantly raising the potential of the combinatorial biosynthesis field in the last decade.
Complementary to chemical synthesis and microbial fermentation, the manipulation of genes governing secondary metabolic pathways offers a promising alternative for preparation of complex Natural Products and their analogs biosynthetically.
Gene clusters encoding many Natural Products have been cloned and characterized, and it is now possible to introduce specific structural alterations into a natural product in the presence of abundant functional groups by rational manipulation of the gene cluster governing its biosynthesis. The resulting molecules can be produced recombinantly by large-scale fermentation.
One of the aspects of our technology is the development of a series of “sugar plasmids”, able to direct the biosynthesis of rare sugars that form part of numerous bioactive compounds of interest in the clinical, agricultural or veterinary markets. Also, we have identified several glycosyltransferases (GTFs) that participate in biosynthesis of bioactive compounds with flexibility in their capacity to recognize and to transfer different sugars.
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