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(BBSRC DTP CASE) Design of a light-driven biocatalyst

  • Full or part time
  • Application Deadline
    Friday, January 31, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Illumination is able to unlock a wide range of photochemical reactions, but light is rarely used by living organisms. In fact, to date only three light dependent enzymes have been described in detail. Nevertheless, there is considerable scope for such reactions given that a range of biological cofactors (such as nicotinamide or flavins) undergo photoredox chemistry under appropriate conditions. Indeed, several groups recently reported the discovery of light-dependent non-natural reactivity with a range of cofactor binding enzymes (1). We seek to develop novel light-dependent enzymes through protein engineering to improve our understanding of how the enzyme protein matrix directs photochemistry. Our immediate targets are decarboxylation reactions of interest to biofuel development, inspired by the discovery of the third natural light-dependent enzyme: fatty acid decarboxylase (2). This enzyme is able to convert fatty acids to the corresponding alkanes + CO2 upon illumination through an as yet ill-understood flavin-dependent mechanism. Making use of a considerable library of flavin-dependent enzymes at the Manchester Institute for Biotechnology (MIB; references 3-4), we will use (rational) enzyme evolution to generate more robust non-natural light-dependent decarboxylases with appropriate substrate specificity.

The PhD student will be based in Department of Chemistry and the Manchester Institute of Biotechnology (MIB) and will be co-supervised by Professor David Leys (synthetic and structural biology), Dr Sam Hay (computational chemistry) in collaboration with our industrial sponsor Shell. The project is interdisciplinary, giving the student the opportunity to gain broad experience in modern experimental biophysics, enzymology, biocatalysis and structural biology alongside biochemically-relevant computational chemistry within an industrially relevant setting.

http://www.mib.ac.uk
https://www.research.manchester.ac.uk/portal/Sam.Hay.html
https://www.research.manchester.ac.uk/portal/david.leys.html

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.

References

1. Biegasiewicz, K.F. et al. (2019) Science, 364, 1166-1169
2. Sorigue, D. et al. (2017) Science, 357, 903-907
3. Leys, D. (2018) Curr. Opin. Chem. Biol. 47, 117-125
4. Leys, D. & Scrutton N.S. (2016) Curr. Opin. Struct. Biol. 41, 19-26

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