A simple-to-use quantum chemistry programme for interpreting the spectroscopy of metalloenzymes and metal-containing catalysts

Background

In 2010, a breakthrough was made in the world of biofuel production. This breakthrough was the discovery of a set of enzymes which are used by bacteria and fungi in the degradation of biomass. These enzymes, lytic polysaccharide monooxygenases (LPMOs), were shown to break down cellulose using a previously unknown oxidative mechanism. The result is that LPMOs boost significantly the conversion of cellulose to sugar when used in concert with other cellulases (in accord with their biological role).¹ 

Objectives

This proposal for a PhD studentship is written in this context. What the past ten years of research on LPMOs has shown is that there is a need for a simple-to-use, chemically intuitive and also theoretically rigorous quantum chemistry programme which is able to link spectroscopic measurements (e.g. EPR, UV/vis, MCD etc) to the structure, identity and function of a metal ion at the active site of a metalloenzyme, and also of small molecule metal complexes/catalysts in general.

Approach 

This studentship seeks to provide such a computer programme. The proposed work will build on that of a previous graduate student who has written Kestrel, a programme² which uses semi-empirical methods developed in the 70-80s for the interpretation of UV/vis, magnetic spectroscopic and magnetic susceptibility measurements for transition metal complexes.³ The programme currently takes as its input the d-electron count of the metal ion, the arrangement of ligands around the metal (from X-ray structure) and so-called ‘e-values’ which reflect directly the bonding of individual ligands to the metal.  

The main idea of the programme is that the e-values are chemically-intelligible (a bit like ‘hybrid’ orbitals in organic chemistry). So, these e-values mean something to the chemist, and he/she can then understand the bonding/reactivity of the metalloenzyme active site though the bonds the metal makes to the surrounding amino acids. Kestrel’s current output gives EPR g values, d-d transition energies and magnetic susceptibilities. The proposed studentship will now extend this output to include X-ray absorption transition energies, MCD energies and band intensities and, finally, UV/vis transition intensities of metalloenzymes (LPMOs) and small molecule Cu complexes which can potentially act as catalysts for the same reaction that LPMOs carry out.

Novelty

Importantly, the student will also investigate whether there is a common set of amino acid e-values, but collecting and then evaluating the spectra of several metalloenzymes (including LPMOs). The result will be a complete spectroscopic package from which any chemist/biochemist studying a metalloenzyme will be able to interpret and characterise the associated spectroscopy in a simple, intelligible but highly robust way.

Training

In year 1, the student will acquire skills in the basics of semi-empirical quantum theory, computer programming and spectroscopy (especially MCD and XAS), and also collection of such data for an LPMO enzyme under a variety of conditions (note here that the student will have opportunity to prepare their own LPMO proteins if they wish). Year 2 will concentrate on analysing the data from year 1, and expanding the computer programme to include MCD transition intensities, and possibly XAS transition energies. Year 3 will potentially involve some work at the Diamond synchrotron to collect XAS data on LPMOs. 

1) Faraday Discussions, 2021, https://doi.org/10.1039/D1FD00073J

2) Proc. Nat. Acad. Sci. 2011, 108(37), 15079–15084.  

3) Gerloch, M. Magnetism and Ligand Field Analysis, Cambridge University Press, Cambridge, 1984.

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/training/idtc/

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/. 

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 2023. Induction activities may start a few days earlier.

To apply for this project, submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3

You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject. Please check the entry requirements for your country: https://www.york.ac.uk/study/international/your-country/