Schwefel für die sauerstofffreie Welt: Closthioamid (1), der einzige bekannte sekundäre Metabolit eines streng anaeroben Bakteriums, wurde aus anaerobem Clostridium cellulolyticum (siehe SEM‐Bild) nach Induktion der Biosynthese mit einem wässrigen Bodenextrakt isoliert. Dieser neue Typ eines symmetrischen Naturstoffs, in dem alle Bausteine durch Thioamideinheiten verknüpft sind, hemmt das Wachstum multiresistenter Staphylokokken.

Genetic manipulation of the LuxR-type quorum sensing regulator system in Burkholderia thailandensis caused a significant change in the metabolic profile: it led to activation of the thailandamide biosynthesis gene cluster, dramatically increased thailandamide production, and induced strong pigmentation. A novel polyketide metabolite, thailandamide lactone (2), which cannot be detected in the wild type, was isolated from the mutant broth, and its structure was elucidated by high-resolution mass spectrometry and IR and NMR spectroscopy. In a biological assay using tumor cell lines, 2 showed moderate antiproliferative activities. This finding not only points to complex regulation but also serves as a proof of concept that engineering quorum sensing mutants may enable the discovery of novel bioactive natural products encoded by silent or only weakly expressed biosynthetic pathway genes.

Choose sulfur in an oxygen‐free world: Closthioamide (1) was isolated from the anaerobe Clostridium cellulolyticum (see SEM image) after the induction of its biosynthesis with an aqueous soil extract. An unprecedented type of symmetrical natural product in which all building blocks are connected through thioamide linkages, 1 is active against multiresistant staphylococci. It is the only known secondary metabolite from a strictly anaerobic bacterium.

Decoded before decay: Cryptic and highly unstable polyketide metabolites, thailandamides A and B, were isolated from Burkholderia thailandensis, and their absolute configurations fully elucidated using a combination of chemical degradation, bioinformatics, NMR spectroscopy, precursor‐directed biosynthesis, and analysis of pathway intermediates (see scheme).

Anti‐Terminator: Rise of the Molecules: Overexpression of an antiterminator gene (nusG) in Clostridium cellulolyticum induced the biosynthesis of the novel antibiotic closthioamide and related thioamides. This is the first successful genetic engineering of an anaerobe to trigger a cryptic pathway. Furthermore, synthetic probes provide valuable insights into the biogenetic relationship of the rare thioamide metabolites.