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Probing the redox mechanism of lytic polysaccharide monooxygenases


   Department of Chemistry

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  Dr A Parkin  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Background

The focus of the PhD will be to conduct previously impossible hypothesis-led investigations into the redox chemistry of carbohydrate-degrading copper enzymes (lytic polysaccharide monooxygenases, LPMOs) that play a crucial role in biorefinery enzyme cocktails. The redox chemistry of LPMOs is particularly important due to the unusual ability of these enzymes to break down highly stable substrates such as cellulose and chitin under mild conditions of aqueous solvent, near-neutral pH, and room temperature. The sugar substrates produced by LPMOs can be used as sustainable feedstocks for renewable fuel production.

Objectives

The aim of the project is to relate LPMO amino acid sequence to reactivity using the Parkin group’s specialised in-house electro-enzymology methods. In enzyme electrochemistry, the direct measurement of electrical current directly reports on the rate of electron flow as a function of energetic (potential) driving force. This is a combination of thermodynamic and kinetic mechanistic insight which is otherwise inaccessible via spectroscopy, crystallography or microscopy techniques meaning that bio-electrochemistry measurements play a vital role in complementing other techniques, moving beyond insight into what an enzyme looks like and providing vital measurement of the reactivity. This PhD research will be part of a wider project called “Enzyme e-map” that aims to develop a powerful, new enzyme electrochemistry toolkit. The PhD student will be trained to develop a new electrochemical toolkit and use complementary molecular biology and protein production techniques to answer critical mechanistic questions about LPMOs and enable new understanding of the link between the structure and function of different LPMOs. Particular controversy exists over whether the LPMO copper active site has evolved to function optimally using two electrons and one O2 as co-substrates in the glycosidic bond cleavage reaction, or whether H2O2 is a more efficient redox-equivalent co-reagent (O2 + 2e- + 2H+  H2O2). The function of different active site residues in tuning catalysis is not known and the electron-transfer “wiring” is also unclear, with speculation over the role of amino acids as reaction partners in the redox reaction. This means we cannot currently select what co-reagents an LPMO requires to perform optimally, and it is unknown how to relate the DNA sequence of the different enzyme subclasses to proposed reaction mechanisms.

Experimental Approach

1. Quantifiably compare the redox reactivity of different LPMOs

2. Synthesise small carbohydrate substrate mimics using commercial sugar building blocks

3. Use molecular biology to probe the relationship between structure and function

Training

The Parkin lab space forms part of the world-class “York Structural Biology Laboratory (YSBL)” suite of facilities (YSBL was awarded the 2019 Queen’s Anniversary Prize for pioneering work in protein molecule research). Parkin is based in the YSBL Chemical Biology lab, with dedicated chemical/enzymatic synthesis, molecular and microbial biology facilities, anaerobic glove box chambers, gas mixing lines and an expert biochemistry technician. The lab is close to the Departmental Glassblowing, Electronic Engineering and Mechanical workshops, and the Departmental Mass-Spec, EPR and NMR facilities. The University’s Bioscience Technology Facility is staffed by skilled research officers who train users on the equipment. As part of the wider “Enzyme e-map” project, the PhD Studentship is supported by travel costs to ensure that the scientific output of the project is well disseminated through conference talks, and also so that the individual researchers can build a strong track record and make personal contacts to facilitate optimal problem-solving in their work and future career progression. All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/cdts/

Equality, Diversity and Inclusion

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/.

Further Information

You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject.  

For more information about the project, click on the supervisor's name above to email the supervisor. For more information about the application process or funding, please click on email institution

This PhD will formally start on 1 October 2022.

To apply for this project, submit an online PhD in Chemistry application:

https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3


Funding Notes

Fully funded for 3.5 years by a European Research Council Consolidate Grant and covers: (i) a tax-free annual stipend at the standard Research Council rate (£16,062 for 2022-23), (ii) tuition fees at the UK/Home or overseas rate, (iii) funding for consumables.
Funding for this project is guaranteed by UK Research and Innovation (UKRI).

References

Candidate selection process:
• You should hold or expect to receive at least an upper second class degree in chemistry or a chemical sciences related subject
• Applicants should submit a PhD application to the University of York by 8 August 2022
• Supervisors may contact candidates either by email, telephone or web-chat for an interview
• Candidates will be notified of the outcome of the decision by email

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