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(BBSRC DTP) Discovery, development and application of novel amine and imine biocatalysts for the synthesis of natural products, their analogues and other privileged motifs

Project Description

This is a cross-disciplinary project, which combines the complementary research expertise of Professor Nick Turner (biocatalysis), Professor Perdita Barran (mass spectrometry) and Dr Roger Whitehead (organic synthesis/biological chemistry). There are two principal goals to the project:
(i) to develop, expand and exploit the available “toolbox” of engineered biocatalysts that are able to either generate imines/imines ions from the corresponding amines (amine oxidases) or alternatively convert imines/iminium ions to enantiomerically pure amines and other more functionalised molecules (imine reductases);
(ii) to develop efficient preparative synthetic approaches for the generation of specific substrates for these biocatalysts – this will ultimately lead to novel chemo-enzymatic routes to privileged structural building blocks as well as bio-active natural and unnatural products.
A structured research programme has been designed with three principal objectives in mind:
• to provide a PhD student with ‘state-of-the-art’ training in the combined fields of advanced organic synthesis, structural data analysis, biocatalyst discovery and development, high throughput screening and advanced mass spectrometry.
• to demonstrate the extensive potential of the two enzyme classes, both individually and in tandem, as versatile catalysts for preparative scale chemical reactions, many of which are difficult, if not impossible, to carry out using traditional synthetic techniques;
• to ultimately provide scientists in a range of chemical and biological research fields (both academic and industrial) with efficient and ecologically friendly routes to important structural types which would otherwise be difficult, if not impossible, to obtain.

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.


1. Negative cooperativity in NAD(P)H quinone oxidoreductase 1(NQO1) Megaroty, C.F.; Bettley, H A-A.; Caraher, M.C.; Scott, K.A.; Whitehead, R.C.; Jowitt, T.A.; Gutierrez, A.; Bryce, R.A.; Nolan, K.A.; Stratford, I.J.; Timson, D.J. ChemBioChem 2019 (Accepted Article) 10.1002/cbic.201900313
2. Eeyarestatin Compounds Selectively Enhance Sec61-Mediated Ca2+ Leakage from the Endoplasmic Reticulum Gamayun, I.; O’Keefe, S.; Pick, T.; Klein, M-C.; Nguyen, D.; McKibbin, C.; Piacenti, M.; Williams, H.M.; Flitsch, S.L.; Whitehead, R.C.; Swanton, E.; Helms, V.; High, S.; Zimmermann, R.; Cavaié, A. Cell. Chem. Biol. 2019, 26 (4), 571.
3. Transition metal-free, visible-light mediated synthesis of 1,10-phenanthroline derived ligand systems Edwards, A.C.; Geist, A.; Müllich, U.; Sharrad, C.A.; Pritchard, R.G.; Whitehead, R.C.; Harwood, L.M. Chem. Commun., 2017, 53, 8160
4. Biocatalytic N-Alkylation of Amines using either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades. J. Ramsden, R.S. Heath, S. Derrington, S.L. Montgomery, J. Mangas-Sanchez, K.R. Mulholland and N.J. Turner, J. Am. Chem. Soc., 2019, 141, 1201-1206.

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