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Design and Engineering of Light-activated Enzymes for Chemicals Production


   Department of Chemistry

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  Prof N Scrutton  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

In this PhD studentship, we will pioneer generalized, rule-based design of photo-biocatalysts to open up new and high-energy catalytic reaction pathways. This will give broad access to difficult-to-achieve reactions, through protein engineering and de novo peptide design, in ways that are not possible using established directed evolution and enzyme engineering workflows. We will deliver first-of-a-kind flavin-based photo-enzymes, bringing photo-biocatalysis into the biological mainstream and expand reaction space well beyond that available with natural enzymes.  

We are taking a unique interdisciplinary approach to decipher mechanistic rules that will enable us to repurpose any flavin-containing enzyme as a photo-biocatalyst through ‘top-down’ engineering of natural enzymes and ‘bottom up’ de novo design of robust photobiocatalytic frameworks. In doing so, we will maintain and expand the beneficial, highly selective, natural and engineered specificities of thermally activated enzymes, which provides major advantages over the limited photocatalytic transformations that can be achieved with small molecule photocatalysts. Fundamental mechanistic understanding of flavin-containing photo-biocatalysts will emerge, coupled with data-driven inferences derived from the sequences, structures and functional properties of natural and engineered proteins.

As such our work will define ‘minimal photocatalytic units’, which can then drive generalized, and data-driven, design/engineering of new photo-biocatalysts, which will impact widely on industrial biocatalysis, cell-factory engineering, nanoscale-device construction, photocatalytic diagnostics and related applications.

The student will explore flavin dependent photocatalysts to obtain mechanistic and structural information using a range of biochemical, biophysical and computational techniques and protein engineering methods. Understanding of photochemistry and how this couples to biocatalysis will is a major focus of this PhD project.

The studentship is part of a larger programme grant on photoactivated biocatalysis led by the Scrutton group and involving collaborators at the University of Manchester, Bristol and Edinburgh. We are looking for motivated students with interests in studying for a PhD in photobiocatalysis, with interests in protein structure and function, biophysics and biocatalysis. The studentship 

 Training and Team: The programme is highly interdisciplinary. Training in protein engineering and protein design, biophysical studies, and time-resolved solution spectroscopy (absorption/fluorescence/IR) will be provided in the group of Prof Nigel Scrutton (Manchester Institute of Biotechnology/Department of Chemistry) and Dr Derren Heyes (MIB Biophysics Facility) and Dr Samantha Hardman (MIB Laser Spectroscopy). Opportunities for training in computational chemistry are also available. The project sits in a larger programme of work funded by BBSRC involving the groups of Prof Perdita Barran, Manchester (MIB/Chemistry mass spectrometry), Prof Dek Woolfson, University of Bristol (protein design) and Dr Chris Wood, Edinburgh (structural informatics and data science) 

Scrutton group website: https://sites.google.com/site/scruttonlab/

http://www.chemistry.manchester.ac.uk/study/postgraduate/researchdegrees/howtoapply/

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact. We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

 We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder). 


Funding Notes

This studentship covers the fees (UK students), basic stipend and consumables for a 3.5 year PhD project.

References

1. D. Sorigué, et al. (2017) Science 357 903-907
2. M. Amer, et al. (2020) Energy Environ. Sci.
3. B. Lakavath, et al. (2020) Anal. Biochem. 600 113749
4. D. J. Heyes, et al. (2020) ACS Catal. 6691-6696

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