DZIF

Innovative microbial resources for new anti-infectives

01/01/2016 to 31/12/2018

The Tübinger strain collection includes a large number of proven producers of interesting compounds, which have not been followed up. So far, these strains were only grown in standard production media and no effort has been made to analyse their full biosynthetic capabilities. We plan to develop methodes to exploit this potential. On one hand, we will simulate those growth conditions in the environment in which natural product synthesis is required for survival. Those conditions should induce expression of specific biosynthetic genes in the genome of bacteria. On the other hand, we will apply a genetic approach. In previous years we have characterized a large number of regulators which induce the expression of biosynthetic gene clusters encoding compounds of differentstructures and mode of action. we will set up a "regulatory gene bank" which will be transferred into producers of the Tübinger strain collection. Induction of natural product synthesis will be monitored either on product level and/or on gene expression level usind reporter systems. These approaches driven by microbiological and genetic techniques will enable the exploitation of the huge sleeping potential of the strains of the Tübinger collection.
A special effort will be made to develop a robust reporter system for antibiotic production. Ideally this system should allow to detect the production of antibiotics, while the fermentation process is still ongoing. Promotors are known from previous large-schale transcriptome studies that are selectively induced upon stresses actiog on different bacterail metabolic pathways. So far, such reporter strains have been employed predominately for mode of action studies of antibacterial agents, providing first ideas on the metabolic pathway affected. Here, we suggest exploiting reporter strains to monitor production of antibiotic substances to screen for isolates that produce antibacterial agents and to select conditons favorable for antibiotic production. In a feasibility study we propose to construct and use a panel of reporter strains in the screening effort of the Tübingen strain collection.