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A biosynthetic platform for plant-derived therapeutics: enzymatic production of novel flavonoids as potential anti-inflammatory drug candidates


Department of Chemistry

Manchester United Kingdom Analytical Chemistry Biochemistry Bioinformatics Biotechnology Molecular Biology Structural Biology

About the Project

Inflammation is involved in a vast number of diseases, and often underlies chronic pain, a debilitating condition affecting over 1.5Bn people worldwide. Since a large proportion of non-steroidal anti-inflammatory drugs (NSAIDs), and other painkillers such as opioids, can have serious side effects there is a need for safe and effective new anti-inflammatory drugs to treat this growing market.

Plant derived flavonoids are particularly attractive as powerful anti-inflammatory drug candidates, however, they are typically found in minuscule amounts in plants. Extracting and purifying these compounds from the plant is simply not feasible. This project seeks to develop anti-inflammatory drug candidates through the use of biotechnology, using plant material as a feedstock.

The principal objectives of the project are:

1. Develop robust biosynthetic routes to derivatized flavonoid skeletons

2. Optimise routes from ‘feed-in’ flavonoid precursors, or primary building blocks

3. Create a library of derivatized flavonoids for bioactivity screening

The candidate molecules will be tested at the sponsor company Phytome Life Sciences on industry relevant models of inflammatory diseases, with expectations of real-life applications in their outcomes.

Training opportunities

This project offers exposure to cutting edge technologies in synthetic biology, metabolic engineering, biocatalysis, biosynthesis, and cell and molecular based assay systems in an academic and commercial setting.

About Phytome Life Sciences

Phytome Life Sciences is a contract research organisation focused on the development of innovative manufacturing and pharmaceutical technology platforms for the advancement of plant-based medicines.

About the Future Biomanufacturing Research Hub

An EPSRC & BBSRC funded UK biotechnology programme that brings together academic and industry capabilities to accelerate the development of sustainable bio-based manufacturing in four key sectors:

Pharmaceuticals | Value-added chemicals | Engineering materials | Advanced biofuels

To learn more please visit: https://futurebrh.com/

Academic background of candidates

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in molecular biology / biotechnology / chemistry / biochemistry or a related subject. A Master’s degree in a relevant subject is desirable. 

Contact for further Information

Professor Nigel Scrutton

Dr Kirk Malone


Funding Notes

This 4 year PhD studentship funded by the University of Manchester and Phytome Life Sciences Limited covers fees, an enhanced stipend (£17,609 in 2021-22) and consumables.
Open to UK applicants only.
Available start dates:
July 2021
September 2021

References

1] M. S. Dunstan, C. J. Robinson, A. J. Jervis, C. Yan, P. Carbonell, K. A. Hollywood, A. Currin, N. Swainston, R. Le Feuvre, J. Micklefield, J.-L. Faulon, R. Breitling, N. Turner, E. Takano, N. S. Scrutton. Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol. Synthetic Biology, Volume 5, Issue 1, 2020, ysaa012. DOI: 10.1093/synbio/ysaa012
2] de Bruijn, W. J., Levisson, M., Beekwilder, J., van Berkel, W. J., & Vincken, J. P. Plant Aromatic Prenyltransferases: Tools for Microbial Cell Factories. Trends in Biotechnology, 2020 Aug; 38(8): 917-934. DOI: 10.1016/j.tibtech.2020.02.006
3] Rea, K. A., Casaretto, J. A., Al-Abdul-Wahid, M. S., Sukumaran, A., Geddes-McAlister, J., Rothstein, S. J., & Akhtar, T. A. Biosynthesis of cannflavins A and B from Cannabis sativa L. Phytochemistr, 164, August 2019, 162-171. DOI: 10.1016/j.phytochem.2019.05.009
4] Yang, X., Yang, J., Jiang, Y., Yang, H., Yun, Z., Rong, W., & Yang, B. Regiospecific synthesis of prenylated flavonoids by a prenyltransferase cloned from Fusarium oxysporum. Scientific reports, 2016, 6: 24819. DOI: 10.1038/srep24819

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