About the Project
A PhD studentship is available to work in the group of Professor Nicholas Turner within the Manchester Institute of Biotechnology. This studentships are part of a recently funded ERC Advanced Grant (BIO-H-BORROW) and is funded for up to 3.5 years. The aim of BIO-H-BORROW is to develop a conceptually new biocatalytic approach for amine synthesis in which alcohols are used as universal substrates, ammonia is the source of the amine in the product, and the only by-product of the reaction is water. To achieve this ambitious goal we will develop a series of redox neutral hydrogen-borrowing (HB) cascades involving various combinations of engineered biocatalysts including reductive aminases (RedAms), amine dehydrogenases (AmDHs), alcohol dehydrogenases (ADHs), alcohol oxidases (AOXs) and carboxylic acid reductases (CARs). These enzymes are cofactor dependent (NADH/NADPH/ATP/O2) therefore the aim is to establish cascade processes in which only catalytic amounts of cofactor are used. Having established the viability of these individual catalytic cycles, we will combine them to enable complex amine synthesis from alcohols and ammonia via cascade processes. Key targets for this methodology will be a range of amine containing molecules including pharmaceuticals, agrochemicals and fine chemicals.
The objective of this studentship is to develop optimized hydrogen-borrowing cycles for the synthesis of target chiral amines. AOXs combined with RedAms for alcohol to amine conversion (Year 1). AmDHs combined with ADHs for alcohol to amine conversion; RedAms combined with ADHs for 2o and 3o amine synthesis (Year 2). Design of experiments (DoE applied) to hydrogen-borrowing cycles. Optimised conditions for hydrogen-borrowing cycles (Year 3). Application of immobilized biocatalysts under flow conditions (Year 4).
Informal inquiries can be made to Professor Nick Turner by email ([Email Address Removed]).
Funding Notes
The position is available from September 2018, funded by an ERC Advanced Grant which covers tuition fees and stipend for 3.5 years Applications are invited from UK/EU nationals. Candidates from outside the UK must have resided in the UK for 3 years prior to commencing the PhD to be eligible to apply.
Applicants must have, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject. A Masters Degree in Chemistry, Biochemistry or Biotechnology would be desirable.
Full details on how to apply can be found here: http://www.chemistry.manchester.ac.uk/study/postgraduate/researchdegrees/howtoapply/
References
1) J. Leonard, A.J. Blacker, S.P. Marsden, M.F. Jones, K.R. Mulholland & R. Newton, Org. Process Res. Dev., 2015, 19, 1400.
2) G.A. Aleku, S.P. France, S. Hussain, J. Mangas-Sanchez, F. Leipold, S. Montgomery, H. Man & G. Grogan, Nature Chem., 2017, 9, 961-969.
3) F.G. Mutti, T. Knaus, N.S. Scrutton, M. Breuer & N.J. Turner, Science, 2015, 349, 1525.
4) Juan Mangas-Sanchez, S. Montgomery & N.J. Turner, Angew. Chem. Int. Ed., 2017, 56, 10491-10494.
5) N.J. Turner & E. O'Reilly, Nature Chem. Biol., 2013, 9, 285; M. Hönig, P. Sondermann, N.J. Turner and E.M. Carreira, Angew. Chem. Int. Ed., 2017, 56, 8942-8973.
Continue with Facebook
