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

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.