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Promoter Activation in Δ hfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing
Author(s) -
Bode Edna,
Heinrich Antje K.,
Hirschmann Merle,
Abebew Desalegne,
Shi YanNi,
Vo Tien Duy,
Wesche Frank,
Shi YiMing,
Grün Peter,
Simonyi Svenja,
Keller Nadine,
Engel Yvonne,
Wenski Sebastian,
Bennet Reuel,
Beyer Sophie,
Bischoff Iris,
Buaya Anthony,
Brandt Sophie,
Cakmak Ibrahim,
Çimen Harun,
Eckstein Simone,
Frank Denia,
Fürst Robert,
Gand Martin,
Geisslinger Gerd,
Hazir Selcuk,
Henke Marina,
Heermann Ralf,
Lecaudey Virginie,
Schäfer Wilhelm,
Schiffmann Susanne,
Schüffler Anja,
Schwenk Rebecca,
Skaljac Marisa,
Thines Eckhard,
Thines Marco,
Ulshöfer Thomas,
Vilcinskas Andreas,
Wichelhaus Thomas A.,
Bode Helge B.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201910563
Subject(s) - xenorhabdus , photorhabdus , mutant , gene , computational biology , biology , promoter , chemistry , biochemistry , gene expression
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 Δ hfq 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 easy PACId 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.