Mining and expressing novel antimicrobials from sponge symbionts

Project

Mining and expressing novel antimicrobials from sponge symbionts

Mine deep-sea sponge symbionts, which are “mare incognita” with respect to their bioactive potential, and develop a heterologous expression strategy for the gene clusters producing antimicrobials.

Antibiotic resistant (ABR) bacteria are estimated to cause >25,000 deaths annually in Europe alone, and the ABR problem is intertwined with the decreasing discovery rate of new antimicrobials. Marine sponge-associated bacteria excrete a plethora of metabolic compounds with potential as novel clinical antimicrobials, and important enzyme complexes producing these natural drug candidates are non-ribosomal peptides synthetases (NRPS), type I polyketide synthases (PKS), and ribosomally synthetized and post translationally modified peptides (RiPPs). These complexes are often coded by several genes placed together in the chromosome, constituting Biosynthetic Gene Clusters (BGC).

We have screened several sponge samples and selected a number of BGC candidates for heterologous expression. This project aims to develop a heterologous expression strategy for the gene clusters producing the antimicrobials, thus creating a novel production platform for targeted compounds originating from uncultivable microbes. Activities involve biosynthetic gene cluster DNA & protein sequence analysis, design and construction of expression vectors, protein expression & purification assays, preparation of MS samples, amongst others.