Open Access

Edna Bode, Antje Katharina Heinrich, Merle Hirschmann, Desalegne Abebew, Yan-Ni Shi, Tien Duy Vo, Frank Wesche, Yi-Ming Shi, Peter Grün, Svenja Simonyi, Nadine Keller, Yvonne Engel, Sebastian Wenski, Reuel Bennet, Sophie Beyer, Iris Bischoff, Anthony Buaya, Sophie Brandt, Ibrahim Cakmak, Harun Çimen, Simone Eckstein, Denia Frank, Robert Fürst, Martin Gand, Gerd Geisslinger, Selcuk Hazir, Marina Henke, Ralf Heermann, Virginie Lecaudey, Wilhelm Schäfer, Susanne Schiffmann, Anja Schüffler, Rebecca Schwenk, Marisa Skaljac, Eckhard Thines, Marco Thines, Thomas Ulshöfer, Andreas Vilcinskas, Thomas A. Wichelhaus, Helge Björn Bode

• Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non-ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.