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Heterologous expression of natural products from microbes living in a self-sustaining environment

Project description

Characterising novel metabolites produced by lichen in natural environments

Isolated microbes represent only a very small percentage of the microbial diversity in the natural environment. While their study has led to interesting compounds urgently needed for new antimicrobial drugs, the discovery of such compounds has been declining over the last few decades. With the support of the Marie Skłodowska-Curie Actions programme, the FungalHetEx project will investigate lichens, a microbial community including fungi, green algae, cyanobacteria and bacteria. A recent study harnessed high-throughput technologies and multiomics analyses to facilitate the challenging study of lichens in their natural environment. Building on this knowledge, FungalHetEx aims to apply synthetic biotechnology, bioinformatics, chemistry, and microbiology techniques to characterise novel metabolites produced from symbiosis in lichen communities.

Objective

The increases in antimicrobial resistance and infections caused by microbes, such as mucormycosis (black fungus disease) on Covid-19 patients, highlight the urgent need for new antimicrobial drugs. Most drugs approved for clinical use are based or inspired by natural products. The recurrent re-discovery of compounds when studying isolated microbes, declined the research on natural products in the last decades. However, isolated microbes represent a small percentage of the true microbial diversity living in the environment. Lichens are a microbial community formed by different partners (fungi, green algae, cyanobacteria, bacteria) and their metabolites present diverse biological activities including antimicrobial. Furthermore, many of these molecules have vibrant colours and can be used as natural colorants. Due their slow growth and difficulties in the laboratory cultivation, little is known about natural products biosynthetic genes of the multiple partners living in symbiosis. The improvement in high-throughput technology and the current affordable prices for multi-omics analysis (meta-genomics, -transcriptomics and -bolomics), are allowing a deeper study on natural environmental samples. This project aims to use the knowledge obtained in a recent multi-omics study and apply synthetic biotechnology, bioinformatics, chemistry and microbiology techniques to study novel metabolites from lichen. Polyketide synthase biosynthetic gene clusters have been selected and they will be cloned, transformed and heterologously expressed using Aspergillus oryzae. The optimisation of the polyketides biosynthesis by the heterologous host will be performed and different fermentation conditions will be tested. Novel molecules will be chemically and biologically characterized. During FungalHetExt, I will study novel molecules produced under symbiosis using a multidisciplinary approach with the focus to discovery new molecules and improve my science communication and leadership skills.

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Topic(s)

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Funding Scheme

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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-2022-PF-01

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Coordinator

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
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.

€ 254 330,40
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands

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