Many bacterial species produce secondary metabolites that are not essential for their growth but provide advantages in environmental adaptation, e.g. by serving as signalling molecules that mediate interspecies interactions. Most of the studied bacterial secondary metabolites have biological activity and some have been developed into drugs, such as antibiotics and anticancer agents. Advances in bacterial genomics, metagenomics, and analyses of the secondary metabolite biosynthesis pathways revealed huge potential of certain species to produce compounds that could never be revealed in the laboratory-based cultivation of single isolates. Genes for the biosynthesis of secondary metabolites are organized in clusters, most of which are “silent” under laboratory conditions, and environmental signals triggering their expression remain largely unknown.

Recent studies demonstrate that co-cultivation of bacteria stimulates production of novel secondary metabolites never before detected in the monocultures. Furthermore, members of bacterial phyla abundant in the environment such as Acidobacteriota and Verrucomicrobia but underrepresented by isolated strains harbour many novel biosynthetic gene clusters for secondary metabolites. In MetaBac, we will harness the microbiota of selected eukaryotic hosts (such as a fresh-water bryozoan) and environments as source for the production of novel secondary metabolites.

We will:

  1. analyze metagenomes, metatranscriptomes and metabolomes of selected host-associated and environmental microbiomes;
  2. establish monocultures and defined, simplified microbial communities (synthetic microbiomes) from host-associated and environmental microbiomes
  3. study the biosynthesis of secondary metabolites by defined communities and co-cultures
  4. identify and characterize produced secondary metabolites.

This project aims to create defined, fully tractable microbial communities that produce novel secondary metabolites. The newly developed and systematic approach will be fully transferable to other host-associated and environmental microbiomes, providing a novel microbiome prospecting tool for drug discovery and enabling further investigations into the biological roles of secondary metabolites.