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(BBSRC DTP) Using light to drive chemistry in a natural light-activated enzyme for use in microbial cell factories for chemicals production


   Department of Chemistry

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  Prof N Scrutton, Dr Derren Heyes, Prof Sam Hay  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This project will exploit field-leading biophysical techniques to uncover mechanisms of photocatalysis in flavoenzyme photo-biocatalysts known as fatty acid photodecarboxylases (FAPs).1 These are recently discovered enzymes and they offer a timely entry into generalised photo-biocatalyst engineering by providing exciting new opportunities in industrial biotechnology for the sustainable production of biofuels.2 FAPs convert long chain (C16-18) fatty acids to alkanes / alkenes and although the FAP substrate scope is constrained by the architecture of the substrate-binding pocket, FAP variants can work with shorter chain fatty acids.2 However, one significant drawback of FAP-based photocatalysis is photoinactivation, which is not fully understood but is magnified in FAP variants with altered active site structure, or with substrates that do not bind optimally.3

 Specifically, the student will examine the architecture of the active site of FAP by producing engineered proteins that aim to alter the substrate specificity of the enzyme towards shorter chain substrates. In addition, they will aim to discover new relationships that control off-pathway photoinactivation and use this to learn how ‘reactive geometries’ steer conversion along a productive photocatalytic pathway for non-native substrates. The student will use a range of biophysical and computational approaches to discover how the engineered FAP enzymes catalyse decarboxylation from early stage photochemistry to product formation across a range of timescales.4 This will allow the chemical identity of radical species, reaction mechanisms, knowledge of what determines substrate specificity and identification of localised structural dynamics that may be crucial for catalysis or photoinactivation.  Improved enzyme variants will be integrated into existing microbial strains for scaled chemicals production, particularly in relation to short chain hydrocarbon production. The group has relationships with industrial partners in this area, and the work will be aligned with these partners and the EPSRC funded Future Biomanufacturing Research Hub based in the MIB.

This highly interdisciplinary project is at the cutting edge of enzymology research and will provide the student with expertise in protein engineering methods, protein expression / purification, biochemical assays, computational chemistry and various laser spectroscopy techniques. Additionally, there will be opportunities to gain experience in the scaled production of chemicals using engineered microbial strains and improved variants of the enzyme.

https://sites.google.com/site/scruttonlab/

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

How To Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships    

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/


Funding Notes

Funding will cover tuition fees and stipend only. This scheme is open to both UK and international applicants. However, we are only able to offer a limited number of studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. D. Sorigué, et al. (2017) Science 357 903-907, An algal photoenzyme converts fatty acids to hydrocarbons
2. M. Amer, et al. (2020) Energy Environ. Sci. Low carbon strategies for sustainable bio-alkane gas production and renewable energy.
3. B. Lakavath, et al. (2020) Anal. Biochem. 600 113749, Radical-based photoinactivation of fatty acid photodecarboxylases.
4. D. J. Heyes, et al. (2020) ACS Catal. 6691-6696, Photochemical mechanism of light-driven fatty acid photodecarboxylase.

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