FindA University Ltd Featured PhD Programmes
Engineering and Physical Sciences Research Council Featured PhD Programmes
University of Sheffield Featured PhD Programmes
FindA University Ltd Featured PhD Programmes
FindA University Ltd Featured PhD Programmes

Programmable Enzymatic Synthesis of Bioactive Compounds


Project Description

The aim of this project is to devise a conceptually novel and general platform that will deliver a step-change in complexity of de novo biosynthetic pathways by moving from manual to automated design, build and test. We have identified three bottlenecks that will need to be overcome to build an effective ProgES platform i. Increasing the diversity of structures accessible through biocatalysis by incorporation of C-H activation for early and late stage functionalisation. ii. Fast analytical methods to improve throughput and timescale. iii. A dedicated bioinformatics platform that can harness the technology already developed for chemical and biochemical synthesis and incorporate them into an effective tool for automation for de novo biosynthesis. As proof of principle the ProgrES platform will be used to generate a diverse library of imino sugars of unprecedented complexity.

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in chemistry, biochemistry or a related science. A Masters degree in a relevant subject and/or experience in bioinformatics or biocatalysis is desirable.

Contact for further Information:
Professor Sabine Flitsch
http://www.flitschlab.com

Funding Notes

This is a 4 year PhD studentship funded by an EC ERC Advanced Grant. The funding will cover tuition fees, stipend (£15,009 in 2019) and consumables.
Restricted to UK/EU applicants only.
We expect the programme to start in September 2019.

References

France, Scott P; Hepworth, Lorna J; Turner, Nicholas J; Flitsch, Sabine L; “Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways.” ACS Catal., 2017, 7(1), 710-724. DOI: 10.1021/acscatal.6b02979
France, Scott P.; Hussain, Shahed; Hill, Andrew M.; Hepworth, Lorna J.; Howard, Roger M.; Mulholland, Keith R.; Flitsch, Sabine L.; Turner, Nicholas J. “One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts”. ACS Catalysis (2016), 6(6), 3753-3759. DOI:10.1021/acscatal.6b00855
Hepworth, Lorna; France, Scott; Hussain, Shahed; Both, Peter; Turner, Nicholas; Flitsch, Sabine. De Novo Enzyme Cascades in Whole Cells for the Synthesis of Chiral Cyclic Amines.” ACS Catalysis, 2017, 7, 2920-2925. DOI: 10.1021/acscatal.7b00513
Sardzik, Robert; Green, Anthony P.; Laurent, Nicolas; Both, Peter; Fontana, Carolina; Voglmeir, Josef; Weissenborn, Martin J.; Haddoub, Rose; Grassi, Paola; Haslam, Stuart M.; Widmalm, Goran; Flitsch, Sabine L. “Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 134(10); 4521 – 4524. DOI 10.1021/ja211861m – MAR 14 2012
Both, H. Busch, P. Kelly, F. G. Mutti, N. J. Turner, S. L. Flitsch, Sabine J. “Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions”. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION., 55; 1511 – 1513.DOI: 10.1002/anie.201510028– JAN 22 2016
Contact for further Information
Name of academic, email address, web-site etc
Professor Sabine

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