Project description
Unlocking hidden natural products from microbial dark matter
Since most bacteria do not grow in labs, a vast world of ‘microbial dark matter’ remains hidden, limiting our discovery of next-generation medicines and biotechnologies. Supported by the Marie Skłodowska-Curie Actions programme, the NewRiPPMaturases project is focusing on ribosomally synthesised and post-translationally modified peptides (RiPPs). It will combine bioinformatic mining to find novel RiPP gene clusters with heterologous expression to produce the compounds. The project will map this unchartered genetic space. Finally, biochemical assays will explain how the unusual biosynthetic enzymes (RiPP maturases) drive the process, unlocking powerful new biological tools.
Objective
Studying secondary metabolites from bacterial sources has provided us with many essential medicines and biotechnologically valuable enzymes that construct these highly complex molecules. However, only a handful of talented, chemically rich bacterial producer taxa are the source of these compounds. Identifying new talented producers has been hampered by the as-yet unculturable nature of most bacteria, thus exploring this ‘microbial dark matter’ to identify new bioactive compounds and enzymology is an outstanding challenge.
The Piel lab, in collaboration with several other research groups across several studies, has recently identified a vast number of new and chemically rich and diverse BGCs from 'Entotheonella' and Acidobacteria that are sponge and coral symbionts, respectively. These producers contain a plethora of unusual, putative biosynthetic gene clusters (BGCs) for ribosomally-synthesised post-translationally modified peptides (RiPPs). These are a largely untapped natural product superfamily, found in all domains of life, that feature unprecedented enzymology to generate highly modified and structurally complex bioactive peptide products with numerous indications. Biochemical studies into RiPPs, in particular from 'Entotheonella', has identified RiPP maturases with both previously unknown mechanisms and biotechnological applications, thus highlighting the potential of investigating RiPP pathways from microbial dark matter.
NewRiPPMaturases will explore the RiPP BGCs from 'Entotheonella' and Acidobacteria, a fraction of which have only been previously studied, to expand the repertoire of RiPP natural products and RiPP maturase biochemistry. This will be achieved using a combination of bioinformatic workflows for identifying unusual RiPP gene clusters with high confidence, characterisation of RiPP compounds produced using heterologous expression, and biochemical studies into the substrate profile and mechanism of the unusual RiPP maturases.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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8092 Zuerich
Switzerland
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