Reprogramming Polyketide Biosynthesis to Convert Renewable Carbon into High-Value Natural Products

The EPSRC and BBSRC Centre for Doctoral Training in Negative Emission Technologies for Net Zero (CDT in Net2Zero) is an equal partnership between Aston University (lead), University of Nottingham, Queen’s University Belfast, and University of Warwick. Through cutting-edge research and interdisciplinary collaboration, this CDT aims to tackle global challenges related to climate change and sustainability. 

Our four-year doctoral programme is training the next generation of research leaders tasked to remove greenhouse gases from the environment.  The CDT in Net2Zero focuses on the use of biomass to replace fossil fuels and removal (or capture) of CO2 from the atmosphere, with the potential to create new sources of fuels and chemicals. The centre’s expertise covers Direct Air Capture and CO2 Storage (DACCS), CO2 utilisation, biochar synthesis and utilisation, biomass transition to materials and chemicals, and biomass to energy with carbon capture and storage (BECCS) etc.

Through our research training programme, you will be able to: 

• Develop a network with doctoral researchers, academia, government and industry.
• Access to cutting-edge facilities and opportunities for international collaboration, preparing you for a successful career in academia, industry, or policymaking.
• Carry out a training programme covering practical engineering, communication, entrepreneurship, and business skills to prepare students for diverse sectors.
• The CDT facilitates direct contact between students, industrial partners, policy makers, and third sector organisations to support future careers. You will have the opportunity of a three-month placement with industry, research collaborators or policymakers.

Overview and Background 
 

Fungi are prolific producers of bioactive natural products that find a wealth of applications in medicine and agriculture. Among these metabolites, polyketides represent a particularly diverse and valuable class that include antibiotics, immunosuppressants and agrochemicals. These compounds are assembled by large multidomain enzymes known as polyketide synthases (PKSs), which operate as highly programmed molecular machines. PKSs share a catalytic logic with fatty acid biosynthesis, building complex carbon frameworks through iterative condensation reactions using malonyl-CoA as an extender unit. Because malonyl-CoA is derived from central metabolism through carboxylation reactions, polyketide biosynthesis is intrinsically linked to cellular carbon assimilation. Harnessing and redirecting these biosynthetic pathways therefore offers an opportunity to couple the sustainable utilisation of carbon resources with the production of valuable chemicals.

Recent advances in enzymology, structural biology and synthetic biology have begun to reveal how PKSs control chain length, reduction state and stereochemistry during assembly. A growing body of knowledge within our group has identified key determinants governing this programming, opening the possibility of rationally re-engineering these enzymes to generate new molecular architectures. Such approaches could enable the sustainable biosynthesis of high-value natural product derivatives that currently require complex multistep chemical synthesis.

This project aims to reprogram fungal polyketide biosynthetic enzymes to produce novel or improved analogues of bioactive natural products. Guided by mechanistic and structural insights, specific catalytic domains will be engineered to alter chain extension and modify the structures of the resulting metabolites. The engineered biosynthetic pathways will then be expressed in a heterologous fungal host, Aspergillus oryzae, which is capable of growth on lignocellulosic biomass. By combining enzyme engineering with renewable feedstocks, this work seeks to establish sustainable routes to valuable natural product derivatives while also expanding our ability to re-programme polyketide biosynthesis.

Supervisors: Dr Matthew Jenner, Dr Fabrizio Alberti

Contact information

For any enquiries about this project, please contact the Net2Zero CDT team

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

Person Specification

• A strong foundation in biological / biochemical discipline with First or Upper Second-Class honours degree (or an equivalent qualification from an overseas institution).
• Experience of working in a biological laboratory environment.
• Experience / knowledge of standard molecular biology / biochemical techniques, including: microbial cultivation, genetic manipulation, protein overproduction and purification, enzyme assays, metabolite extraction.
• Excellent organisational and communication skills.
• Strong motivation for curiosity-driven research.

Equality, Diversity and Inclusion is at the heart of the Net2Zero CDT and we know diversity fosters creativity and innovation. We are committed to equality of opportunity, to being fair and inclusive, and to being a place where all belong.

We therefore particularly encourage applications from candidates who are likely to be underrepresented in a higher education setting. These include people from Black, Asian and minority ethnic backgrounds, disabled people, LGBTQI+ people, and women.

• Four-year studentships with a tax-free stipend at UKRI rate (£21,805 per year for 2026/27)
• Paid tuition fees
• A generous research training support grant.

This opportunity is only available to applicants who qualify for home fee status. You can find the rules for home fee eligibility.

Applications for this project from international candidates will not be considered.

Submitting an Expression of Interest

When submitting the Expression of Interest, we will need some information from you, we will be asking about:

1. Your personal details for processing the application.
2. A copy of your passport and, where relevant, include evidence of settled or pre-settled status.
3. Your personal characteristics, for monitoring purposes only.
4. Your Academic background.  We will require English language copies (or screen captures) of the transcripts and certificates for all your higher education degrees, including any Bachelor's degrees.
5. If English is not your first language, you will be required to present evidence that you meet the English Language requirements. You can submit the evidence at a later stage.
6. Your research background and experience.
7. Expressions of interest will be assessed against the following criteria:
   1. Candidate’s motivation and experience: The extent to which the candidate’s expertise, experience, and ambitions align with the goals of the Net²Zero CDT programme.
   2. If you are shortlisted, you will have the opportunity to meet the potential supervisors.

If, after formal interviews, you are offered a place in the training programme, you will be required to submit a formal application within the Home Institution (Aston University, University of Nottingham, University of Warwick, or The Queen’s University of Belfast)

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.