Project description

Primary supervisor - Dr Amr El-Demerdash

Many natural products (NPs) show remarkable biological activity, yet their clinical potential is often limited by poor solubility, metabolic instability, or toxicity. These issues stem from the rigid, hydrophobic, and synthetically challenging frameworks typical of complex NPs. In this project, we aim to overcome these limitations by using biocatalysis, a green and highly selective method to modify natural products at otherwise inert positions. This interdisciplinary project will apply state-of-the-art biocatalysts, including cytochrome P450s, hydroxylases, and flavin-dependent halogenases, to selectively modify three high-value natural products:

• Plumbagin – A naphthoquinone with potent anticancer activity.

• Lithocholic acid – A bile acid with emerging neuroprotective effects.

• Camptothecin – A clinically relevant anticancer agent targeting Topoisomerase I.

In collaboration with Prozomix Ltd. (an industrial leader in enzyme development), this project will:

1. Establish a tailored enzyme panel for site-selective late-stage functionalization of complex NP scaffolds.

2. Optimize biocatalytic reactions to generate a focused library of new NP analogues.

3. Evaluate their anticancer and neuroprotective activities in human cell-based assays.

4. Generate SAR data linking specific enzymatic modifications to pharmacological properties.

This PhD project offers extensive research training in:

• Biocatalysis and enzyme screening.

• Natural product derivatization and purification.

• Analytical chemistry (NMR, LC-MS, HPLC)

• Mammalian cell-based pharmacology.

• Multidisciplinary collaboration (chemical biology and pharmacology).

The student will also undertake a three-month placement at Prozomix Ltd., gaining industrial experience in enzyme production, assay design, and biocatalytic process development. This project is ideally suited for a student with a background in biological chemistry, medicinal chemistry, biochemistry, or related disciplines, and a keen interest in enzyme-enabled drug discovery.

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2025 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP CASE students undertake a three to 18-month placement with the non-academic partner during their study. The placement offers experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team.

This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will be interviewed on 3,4 or 5 February 2026.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/.

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.

To maximise accessibility and attract students from underrepresented groups to our programme we have introduced bespoke templates for applicant Personal and Research statements which will enable every applicant to fully represent themselves through providing suitable examples and evidence. These forms are on the NRPDTP website and must be used for these sections of the application form.

Entry requirements

At least UK equivalence Bachelors (Honours) 2:1. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

Funding

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD CASE studentship with Prozomix Limited. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2025/6 stipend rate: £20,780), and a Research Training Support Grant of £5,000pa for each year of the studentship.

References

Reed, J.*, Orme, A.*, El-Demerdash, A.*, Owen, C., Martin, L.B., Misra, R.C., Kikuchi, S., Rejzek, M., Martin, A.C., Harkess, A. and Leebens-Mack, J., 2023. Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree. Science, 379 (6638), pp.1252-1264.

Liu, Y., Zhao, X., Gan, F., Chen, X., Deng, K., Crowe, S.A., Hudson, G.A., Belcher, M.S., Schmidt, M., Astolfi, M.C. and Kosina, S.M., 2024. Complete biosynthesis of QS-21 in engineered yeast. Nature, 629(8013), pp.937-944.

Martin, L.B., Kikuchi, S., Rejzek, M., Owen, C., Reed, J., Orme, A., Misra, R.C., El-Demerdash, A., Hill, L., Hodgson, H. and Liu, Y., 2024. Complete biosynthesis of the potent vaccine adjuvant QS-21. Nature Chemical Biology, 20(4), pp.493-502.

Jo, S., El-Demerdash, A., Owen, C., Srivastava, V., Wu, D., Kikuchi, S., Reed, J., Hodgson, H., Harkess, A., Shu, S. and Plott, C., 2025. Unlocking saponin biosynthesis in soapwort. Nature chemical biology, 21(2), pp.215-226.

Polturak, G., Misra, R.C., El-Demerdash, A., Owen, C., Steed, A., McDonald, H.P., Wang, J., Saalbach, G., Martins, C., Chartrain, L. and Wilkinson, B., 2023. Discovery of isoflavone phytoalexins in wheat reveals an alternative route to isoflavonoid biosynthesis. Nature Communications, 14(1), p.6977.

Biocatalytic Diversification of Complex Natural Products for Enhanced Therapeutic Performance (EL-DEMERDASH_U26CASE)

Project description

Entry requirements

Funding

References