Objective
The development and spread of antibiotic resistance in microorganisms is a major threat to both humans and animals and the search for new and improved drugs is of high importance. Natural products are experiencing a strong revival as leads in drug development, and biosynthetic engineering offers sustainable routes to new and potentially improved analogues. Finding new ways to make these rational changes should ensure that the European Research Area remains competitive in realising the potential of this technology. The aim of this project is to gain a detailed understanding of a newly-identified family of enzymes supplying unusual fatty acid building blocks for assembly-line biosynthesis of natural products; and to exploit these insights to develop more efficient strategies for targeted alteration of their structures. The novel precursor enzymes to be studied, a ligase and a biotin-dependent carboxylase, are in pathways to several polyketides produced by actinomycete bacteria.
The project divides into three parts. First, additional examples of the new pathway will be sought by targetted whole-genome sequencing, as well as bio-informatic analysis of published sequence databases, and gene knockouts used to confirm the role of the pathway in providing polyketide extender units. Secondly, candidate ligases, carboxylases and the cognate acyltransferase domains that specifically recruit the unusual extender units will be studied in vitro for substrate specificity and for their ability to accept non-natural substrates bearing chemical functionality. Finally, a range of non-natural fatty acids will be fed as precursors to engineered strains designed to produce novel polyketide analogues. This approach should significantly expand the available pool of polyketide diversity. At the same time, the researcher will acquire high-level training in biochemical and chemical biology approaches that will help equip her for a leadership role in research.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences computer and information sciences databases
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
CB2 1TN CAMBRIDGE
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.