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Caryolanes are known as typical plant-derived sesquiterpenes. Here we describe the isolation and full structure elucidation of three caryolanes, bacaryolane A-C (1-3), that are produced by a bacterial endophyte (Streptomyces sp. JMRC:ST027706) of the mangrove plant Bruguiera gymnorrhiza. By 2D NMR, analysis of the first X-ray crystallographic data of a caryolane (bacaryolane C), CD spectroscopy, and comparison with data for plant-derived caryolanes, we rigorously established the absolute configuration of the bacaryolanes and related compounds from bacteria. Bacterial caryolanes appear as the mirror images of typical plant caryolanes. Apparently plant and bacteria harbor stereodivergent biosynthetic pathways, which may be used as metabolic signatures. The discovery of plant-like volatile terpenes in endophytes not only is an important addition to the bacterial terpenome but may also point to complex molecular interactions in the plant-microbe association.

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Strictly anaerobic microorganisms, which represent the oldest living beings on earth, are ubiquitous in the environment and in the intestines of higher organisms. Despite their huge impact on human health, ecology, and industrial biotechnology, surprisingly little is known about the natural product chemistry of the oxygen-free world. [1] Until recently, no antibiotic or any other secondary metabolite was known from anaerobes. Bioinformatics analyses of genome sequences of anaerobes, however, have shown a broad biosynthetic potential, in particular for polyketides and nonribosomal peptides. [2][3][4] A plausible explanation for the meager metabolic profiles is that the limited energy supply under strictly anaerobic conditions causes down-regulation or even silencing of the respective genes in the absence of a particular trigger. [5] For the soil-derived bacterium Clostridium cellulolyticum, the cues were contained in an aqueous soil extract. Only in the presence of this complex additive, C. cellulolyticum cultures produced a highly unusual metabolite, named closthioamide (CTA, 1; Figure 1). [6] CTA has a unique symmetrical structure featuring six thioamide moieties. Apart from its highly unusual structural characteristics, CTA exerts a remarkable antimicrobial potential, in particular against problematic nosocomial pathogens (including MRSA and VRE) at nanomolar concentrations. [6,7] Genetic manipulation of the producing strain allowed the isolation and characterization of seven additional thioamide congeners, which appeared to be shunt metabolites and degradation products of CTA. [8] However, the chemical function of the thioamiderich molecule has remained a mystery. Here we report that CTA acts as a selective metal chelator and disclose the unparalleled architecture of the complex.During our efforts to optimize CTA production rates (typically less than 0.2 mg L À1 ), we obtained increased yields of isolated CTA when adding potassium cyanide to the cultures prior to organic workup. Thus we suspected that a portion of CTA is bound in metal complexes and that the ligand is displaceable by cyanide. Yet, a metal complex of CTA could not be detected in the broth, likely because of the low production rates, poor chromatographic performance, and strong background signals.The structure of the symmetric polythioamide 1 strongly suggests that this compound plays a role as a metal ion ligand, in particular because the overall architecture is reminiscent of biogenetic chelators such as the siderophore desferrioxamine B. [9] In stark contrast to siderophores that bind hard Lewis acids (Fe 3+ ), the occurrence of the high number of sulfur atoms in CTA indicates a preference for soft metal ions. To identify potential metal ions that could bind to CTA, we screened mixtures of CTA and metal salts in methanol by reverse-phase thin-layer chromatography (RP-TLC), taking advantage of the strong UV absorbance of thioamides near 270 nm. By means of this assay we could narrow down the number of potential candidates, with Cu + /Cu 2+ bei...