BRISENZ · Enzymology of Polyketide Biosynthesis
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-09-01 → 2009-08-31
- EU contribution
- €1,241,751
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - BRISENZ (Enzymology of polyketide biosynthesis)
The project involved effort from seven Ph.D. students funded via the MC EST project, supervised by seven academics at the University of Bristol. The focus of the project was to further understand the process of polyketide biosynthesis in bacteria and fungi. Polyketides are a class of natural product produced by bacteria fungi and plants and these compounds often possess potent and useful bioactivities - for example lovastatin which is an anticholesterol compound and the pseudomonic acids which are useful antibiotics active against MRSA. The seven projects aimed to deploy a wide variety of methods including synthetic chemistry, analytical chemistry, structure determination of biomolecules by NMR and X-ray crystallography, molecular biology and proteomics. Overall the project has resulted in the successful training of 7 MC EU fellows to Ph.D. level - thus far 5 of the fellows have obtained their Ph.D.s and the remaining two will submit their Ph.D. theses for examination within the next 3 months. The project has resulted in 15 peer reviewed scientific articles in international journals to date, with more submitted and in preparation. Key scientific highlights include: 1. First development of a series of kinetic assays for Type II iterative PKS enzymes which allow dissection of the individual catalytic steps; 2. First use of the above assays to probe protein protein interactions in Type II PKS; 3. NMR observation of acylated Acyl Carrier Proteins and their changes in structure; 4. Structure determination of ACP bound to a malonyl transferase enzyme; 5. NMR determination of the interaction of a PKS ACP with fatty acyl substrates; 6. Determination of catalytic relationships between Fungal and bacterial iterative PKS proteins; 7. Understanding of citryl CoA formation using high-level QM/MM methods; 8. Understanding of acetyl CoA deprotonation steps by citrate synthase; 9. Understanding the contribution of substrate polarisation in citrate synthase; 10. Development of heterologous expression systems for fungal PKS genes; 11. Understanding oxidative post-PKS reactions in a fungus; 12. Use of synthetic chemical intermediates to probe mupirocin biosynthesis.
Data: CORDIS, © European Union
Project objective
Polypeptides are natural products isolated from plants, bacteria and fungi. These compounds have huge impact as pharmaceuticals and agrochemicals and are key products of large multinational companies. Polypeptides are synthesised in nature by enzyme complexes called polypeptide syntheses (PKS). This project brings together a multidisciplinary group of scientists from the University of Bristol with an established track record of excellent research and training in the PKS area. Seven scientists, including two women, will form a group with the critical mass required to compete with international competition. The BRISENZ project will train seven early stage researchers on a focussed multidisciplinary project to push forward research into the structure, activity and chemistry of PKS with the aim of understanding and exploiting these syntheses for the future rational production of new drugs. The BRISENZ project will be based in the School of Chemistry and Department of Biochemistry at Bristol. Both of these departments have received the highest rating for research achievement and potential in the UK. Both departments have established and proven track records of training Ph.D. students to high standard, through structured research and training within formal Graduate Schools. The individual research projects to be carried out by the EST students will be multidisciplinary and offer the students excellent opportunities for training. The BRISENZ project aims to fulfil demand for qualified Ph.D. graduates from industry and academia and also the demand for high quality training by European students. The project will offer tangible benefits to the BRISENZ researchers, the University of Bristol and the EST students through improved research and training. Another outcome will be improved competitiveness with groups in the USA and Japan, and increased likeliness of future research benefits as the seven trained EST students take up research careers in the EU.
Original text from CORDIS.
Participants
- UNIVERSITY OF BRISTOL · BRISTOL, CLIFTONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union