Over the past years, intensive research has been done in pursuit of the development of nicotinamide cofactor recycling systems in oxidoreductase-catalysed reactions, to reduce the overall cost of biocatalytic systems. However, there is still a need to overcome the challenging drawbacks, such as undesired side-reactions, of using these cofactor-dependent enzymes.
The aim of this project is to design and develop synthetic nicotinamide cofactors (mNADs) to be accepted by oxidoreductase enzymes and thus improve biocatalytic processes. The main objectives are (i) an in-depth understanding of the catalytic mechanism of mNAD-driven regeneration with enoate reductases, (ii) expanding the scope of mNADs to other enzymes through protein engineering, and (iii) a preparative exploitation of the optimised system.
Thus, the initial part of this project will be the synthesis of novel mNADs, obtaining a library to be used with enoate reductases to analyse the enzyme mechanism with these biomimics. Further on, variants of an alcohol dehydrogenase will be engineered to expand the scope of the mNADs to other enzymes. Finally, the system will be optimised for preparative scale through a newly designed mNAD recycling system. An enzyme screening kit is also envisaged to be developed.
The objective of this innovative and timely proposal is to provide training in the multidisciplinary fields of organic chemistry, biocatalysis, molecular biology and protein engineering. This proposal is expected to help the applicant reach a position of professional maturity and start an independent career in academia. Benefits for the European Research Area include a new line of research, and the obtained results will be patented and published in high quality journals, with applications to the industrial sector.
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