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Using novel recombinant nitrilases for continuous flow reactions (HLS/SE/DRFAPP7P/63600)

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  • Full or part time
    Dr Perry
  • Application Deadline
    Applications accepted all year round

Project Description

The conversion of a nitrile (CN) group to a carboxylic acid (COOH) group is a transformation commonly encountered in the manufacture of pharmaceutical intermediates. Using a chemical methodology involves extremes of pH, and stoichiometric addition of acid or base to neutralize the reaction mixture. These very harsh set of conditions may degrade the yield/purity of a product, as well as make its synthesis uneconomic when taking into account the cost of dealing with the waste and side products of the reaction. Nitrilase enzymes are able to perform the same transformation at near neutral pH, and without causing significant waste issues. As part of ongoing research at Northumbria University, we have developed a panel of over 30 nitrilases and mechanistically related nitrile hydratases with a range of substrate specificities. We have also developed a range of techniques to immobilize them enabling their simple separation from reaction mixtures and their use as a stationary phase for substrates to react with in a continuous flow methodology. Additionally we have developed a 3D printed methodology for creating a cheap cassette format for performing biocatalytic flow chemistry experiments at the milligramme to gramme scale. This PhD would investigate the use of our well-characterized nitrile-active enzymes in continuous flow based transformations, both for their potential as predictors of scaled up reactions and for their utility in devising sequential and parallel reaction schemes.

This PhD would suit a chemistry graduate, or a biotechnology graduate with a strong and demonstrable interest in chemistry. An interest in working in a multidisciplinary environment with a group working across the chemistry/biology/fabrication interface is essential.

Informal Enquiries
For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please ensure you quote the advert reference above on your application form.

Eligibility
For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please ensure you quote the advert reference above on your application form.

How to Apply
For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please ensure you quote the advert reference above on your application form.

Funding Notes

This studentship is only open to self-funding candidates. Self-funding candidates are expected to pay University fees and to provide their own living costs. In addition, a ‘bench fee’ will have to be paid to cover project running costs (at a level that will be determined specifically for each project).

References

Probing the Enantioselectivity of a Diverse Group of Purified Cobalt-Centred Nitrile Hydratases
Sander van Pelt, Meng Zhang, Linda G. Otten, Jarle Holt, Dimitri Y. Sorokin, Fred van Rantwijk, Gary W. Black, Justin J. Perry, Roger A. Sheldon, Organic and Biomolecular Chemistry, 2011, Vol 9, No 8, 3011 – 3019
A high-throughput screening method for determining the substrate scope of nitrilases.
Graeme Turnbull, Nicola L. Brown, Meng Zhang, Gary W. Black, David Randall and Justin J. Perry, Chemical Communications, 2015 , 51, 2660 - 2662

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