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combinatorial biosynthesis
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Genetic engineering of antitumoral and antibiotic producing strains:
Recent developments in recombinant DNA technology have enabled rapid advances in the cloning of gene clusters involved in the biosynthesis of many bioactive compounds produced by microorganisms, as well as detailed knowledge of the metabolic pathways of secondary metabolites, allowing rapid development of the combinatorial biosynthesis field in the last two decades.
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.
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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. |
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Altering the glycosylation pattern of bioactive natural products:
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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biocatalysis
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Regioselective manipulation and orthogonal protection of multifunctional compounds:
Modification of only one out of several identical functional groups in a molecule is a fundamental challenge to organic chemists, for example the regioselective modification of polyhydroxy compounds, like sugars and nucleosides.
We have developed a number of enzymatic methods to selectively modify multifunctional compounds by acylation, alkoxycarbonylation and aminoacylation, providing new methods for the synthesis of novel analogues of the parent compounds.
Along the same lines, orthogonal protection strategies enable attachment and cleavage of different protecting groups to multifunctional molecules, and it is a valuable tool for the synthesis of a wide range of hydroxy- and amino compounds.
The adequate arrangement of protecting groups attached to the diamines allow us to prepare valuable orthogonally protected cycloalkane-1,2-diamines and 1,2-amino-alcohols in enantiomerically pure form. The protecting groups bear easily removable susbtituents, which allows to differentiate both functional groups for the modular synthesis of a wide and novel range of derivatives.

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Strain screening for biohydroxylation, ketone reduction and nitrile hydrolysis:
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Our collection allows the screening of biocatalytic activities for an extensive variety of biotransformations, for example biohydroxylation, ketoreduction and nitrile hydrolysis. |
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