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Microbial production of native and recombinant tailor-made enzymes for fine chemicals production

Objectif



This project represents an integrated approach to take benefit of the cell factories to the development of a class of key processes and products in the pharmaceutical and fine chemicals industries: enantiomerically pure compounds. The main goal of this project is the microbial overproduction of native and recombinant tailor-made lipolytic enzymes from Candida rugosa and Rhizopus oryzae to be employed, as catalyst, in target reactions of interest for the production of asymmetric fine chemicals and pharmaceutical intermediates (enantiopure compounds).
The project is focused on a multi-disciplinary vision to integrate biological and biochemical engineering interpretation of cell factories activity as the optimum way to produce higher and specific, reproducible and sustainable quality products by biological systems. The final objective is the optimization of the whole process, from genetic and protein engineering, fermentation and downstream processing to biotransformations, to produce the best tailor-made enzyme for the target reactions. The project will be based on advanced techniques of bioprocess engineering, ranging from on-line monitoring to optimal control, making use of commercial or specially designed instruments, mathematical estimation of variables not measurable on-line, studies on cell physiology, as well as tools of metabolic engineering, mathematical modelling and artificial intelligent techniques in order to maximize yields and to have perfectly well characterised tailor-made enzyme production. Fermentation process will be integrated with downstream processing to obtain a highly purified enzyme.
Enzyme engineering will design adequate enzyme derivatives and their kinetics will be characterised to make an accurate evaluation of each tailor-made enzyme in aqueous and non conventional media. They will also evaluate the optimum operational conditions to design the best reactor configuration from the point of view of stereoselectlvity, activity and stability.
Protein and genetic engineering will be performed in close overlapping to the other parts of the project. This overlapping is strictly necessary to obtain accurate experimental results for using computer models of the proteins. It allows us to understand the molecular aspects of the interaction between the enzyme and different substrates, the evaluation of the effects induced by genetic engineering and the design of recombinant enzymes with improved activity and stability.
These objectives are focused on the precompetitive possibilites of the industrial use of lipase derivatives in the product lon of diltiazem derivatives, resolution of racemic mixtures of target chiral alcohols glycidol derivatives), and synthesis of chiral amines.
There is a strong public pressure to avoid the use of racemic mixtures not only in therapeutical drugs but also in pesticides, so the project will provide improved techniques to obtain pure enantiomers of a variety of compounds using in pharmaceutical and fine chemistry industries. This relevance is reflected by the participation of two industries of different countries in the project.

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Coordinateur

Universitat Autonoma de Barcelona
Contribution de l’UE
Aucune donnée
Adresse

08193 Barcelona
Espagne

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