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

Descripción del proyecto

Caracterización de nuevos metabolitos producidos por líquenes en entornos naturales

Los microorganismos aislados sólo representan un porcentaje muy pequeño de la diversidad microbiana del medio natural. Aunque su estudio ha dado lugar a compuestos interesantes que se necesitan urgentemente para nuevos fármacos antimicrobianos, el descubrimiento de tales compuestos ha ido disminuyendo en las últimas décadas. Con el apoyo de las Acciones Marie Skłodowska-Curie, el equipo del proyecto FungalHetEx investigará los líquenes, una comunidad microbiana que incluye hongos, algas verdes, cianobacterias y bacterias. En un estudio reciente se han aprovechado las tecnologías de alto rendimiento y los análisis multiómicos para facilitar el difícil estudio de los líquenes en su entorno natural. Partiendo de estos conocimientos, en FungalHetEx se pretende aplicar técnicas de biotecnología sintética, bioinformática, química y microbiología para caracterizar nuevos metabolitos producidos a partir de la simbiosis en comunidades de líquenes.

Objetivo

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.

Coordinador

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Aportación neta de la UEn
€ 254 330,40
Dirección
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Países Bajos

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Región
West-Nederland Noord-Holland Groot-Amsterdam
Tipo de actividad
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Coste total
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Socios (1)