Objective
The object of the proposal is the development of methodologies for the biotechnological utilisation of hydroxynitrile lyases (HNLs) as catalysts for industrial enantioselective syntheses. HNLs catalyse the formation of a-hydroxynitriles, important intermediates for the preparation of pharmaceuticals, antibiotics and agrochemicals.
In contrast to resolutions of racemic pairs, where the maximum yield can only be 50%, this enzyme catalysed asymmetric synthesis can provide nearly quantitative yields. Therefore, this process will be of particular relevance for an efficient industrial production. The project addresses the scientific and technical issues involved in making this process possible at the industrial scale.
The enantiopurity of bioactive substances has been recognised to be of utmost importance. As a rule only one of the two enantiomers shows the biological activity desired, e.g. as a pharmaceutical. The mirrorinverted structure is often responsible for severe harmful side-effects.
There is an industrial requirement in the EU for enantioselective syntheses, which will be very important in competitive terms for European companies engaged in the production of intermediates in a rapidly growing world market for enantiomerically pure chemical compounds for pharmaceuticals and agrochemicals.
Development of HNLs for biotechnological use is proposed to be carried out in a multidisciplinary, integrated and task-oriented fashion. Out of the presently known HNLs (which differ with respect to specificity, selectivity and activity) those from Sorghum bicolor, Manihot esculenta and Hevea brasiliensis have been selected for this project.
Genes for the enzymes will be cloned and overexpressed in suitable organisms, they will be fully characterised with respect to their functionality and their 3D structures will be determined by X-ray diffraction methods. By means of site-directed mutagenesis and by chemical modification, combined with enzymatic and structural studies, enzyme variants will be produced, characterised and optimised with respect to the envisaged biotechnological applications. The research will also include the study of biocatalyst performance in organic solvents and of immobilised enzymes. The two industrial partners intend to develop marketable enzymes and proprietary bioprocesses.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences chemical sciences catalysis biocatalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
8010 Graz
Austria
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