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Functional Exploration of Novel Enzymes for Ribosomal Peptide Modification from Uncultivated Symbionts of Marine Invertebrates

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution

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.

€ 292 118,88
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
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Total cost

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