Project description
A sustainable way of producing novel antibiotics
Polyketides are a large class of secondary metabolites from bacteria, fungi and plants with interesting and valuable activities. They are exploited as antibiotics, antifungals and drugs and can be chemically synthesised or produced from biological sources. The EU-funded PrediKSion project proposes to exploit acyltransferase polyketide synthase (AT PKS) enzymes from bacteria as a sustainable way to produce polyketides. To unveil new biosynthetic features in AT PKS, researchers will develop a computational pipeline that will assess the functionality of uncharacterised enzymes. Long term this will lead to the discovery of novel pharmaceutical entities
Objective
Many of the most valuable, yet complex chemicals in society are obtained from bacteria, who use giant, multimodular acyltransferase polyketide synthase (AT PKS) enzyme complexes to make these products. The modular nature of these enzymes holds the promise to engineer biosynthetic assembly lines to produce new, societally relevant products in a benign and sustainable manner. However, the chemical functionalities installed by the textbook cis-AT PKSs is mostly limited to several basic moieties.
In contrast, in a second class of PKSs, trans-AT PKSs, over 150 different module types have been identified, yet with many more still uncharacterized. Initial results show that bioinformatically-guided approaches can be effective ways to assign the functionality of these uncharacterized modules, but only individual examples have been studied. To catalyze the discovery of new functionality in trans-AT PKSs, I propose PrediKSion: a comprehensive, evolution-guided and experimentally validated computational pipeline to unravel the hidden chemical functionality of unassigned trans-AT PKS modules.
PrediKSion will facilitate unbiased discovery of new module functionalities by looking at the phylogeny of ketosynthases (KSs) in the PKS sequences. The high substrate selectivity in KSs reveals crucial information on chemistry installed by upstream modules and can thereby lead to the discovery of new and unexpected biosynthetic features in uncharacterized PKS modules and elusive trans-acting components. PrediKSion will be applied on the complete bacterial tree of life and achieve great impact by providing the community with a global mapping of predicted chemical functionality in trans-AT PKSs. The computational suggestions will finally be validated experimentally and the substrate scope of new PKS modules will be studied. In this way, PrediKSion will accelerate the mapping of uncharacterized PKSs and the discovery of new metabolites and potentially interesting pharmaceutical platforms.
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 biological sciences biological morphology comparative morphology
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2020
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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.
8092 Zuerich
Switzerland
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.