Genome editing in Photorhabdus and Xenorhabdus – Biotechnological application and ecological context

Natural products are molecules produced by living organisms and serve as the foundation of many modern medicines, especially in combating infections. Since the discovery of antibiotics like penicillin, research in this field has developed a wide range of antibiotics, although excessive use has led to resistance. Microorganisms, particularly bacteria, play a central role in natural product research, as they produce these substances in biosynthetic gene clusters (BGCs). Some BGCs, however, remain inactive, as they require specific environmental conditions for activation. This work focuses on the development of genetic tools, specifically a CRISPR/Cpf1 system, to activate gene clusters in bacteria of the Photorhabdus and Xenorhabdus genera. This approach led to the discovery of new natural products and improved their production. Additionally, rare gene clusters found in only a few bacterial strains were investigated. The work also demonstrates that genomically reduced bacterial strains can serve as production systems for natural products, improving the efficiency of bioproduction.