Deuterium-Labeled Precursor Feeding Reveals a New <i>p</i>ABA-Containing Meroterpenoid from the Mango Pathogen Xanthomonas citri pv. <i>mangiferaeindicae</i>

A new <i>para</i>-aminobenzoic-acid-containing natural product from the mango pathogenic organism Xanthomonas citri pv. <i>mangiferaeindicae</i> is described. By means of stable isotope precursor feeding combined with nontargeted LC-MS/MS, the generated spectra were clustered and visualized in a molecular network. This led to the identification of a new member of the meroterpenoids, termed xanthomonic acid, which is composed of an isoprenylated <i>para</i>-aminobenzoic acid. <i>In vitro</i> cytotoxicity assays demonstrated activity of xanthomonic acid against several human cancer cell lines by induction of autophagy

A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides

The marine sponge-derived fungus Stachylidium bicolor 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid N-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (1) and F (2). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V1A receptor, a member of the G protein-coupled receptor superfamily

The <i>O</i>-Carbamoyl-Transferase Alb15 Is Responsible for the Modification of Albicidin

Albicidin is a potent antibiotic and phytotoxin produced by <i>Xanthomonas albilineans</i> which targets the plant and bacterial DNA gyrase. We now report on a new albicidin derivative which is carbamoylated at the <i>N</i>-terminal coumaric acid by the action of the ATP-dependent <i>O</i>-carbamoyltransferase Alb15, present in the albicidin (<i>alb</i>) gene cluster. Carbamoyl-albicidin was characterized by tandem mass spectrometry from cultures of a <i>Xanthomonas</i> overproducer strain and the gene function confirmed by gene inactivation of <i>alb15</i> in <i>X. albilineans</i>. Expression of <i>alb15</i> in <i>Escherichia coli</i> and <i>in vitro</i> reconstitution of the carbamoyltransferase activity confirmed albicidin as the substrate. The chemical synthesis of carbamoyl-albicidin finally enabled us to assess its bioactivity by means of <i>in vitro</i> gyrase inhibition and antibacterial assays. Compared to albicidin, carbamoyl-albicidin showed a significantly higher inhibitory efficiency against bacterial gyrase (∼8 vs 49 nM), which identifies the carbamoyl group as an important structural feature of albicidin maturation

Mass Spectrometry-Based Visualization of Molecules Associated with Human Habitats

The cars we drive, the homes we live in, the restaurants we visit, and the laboratories and offices we work in are all a part of the modern human habitat. Remarkably, little is known about the diversity of chemicals present in these environments and to what degree molecules from our bodies influence the built environment that surrounds us and vice versa. We therefore set out to visualize the chemical diversity of five built human habitats together with their occupants, to provide a snapshot of the various molecules to which humans are exposed on a daily basis. The molecular inventory was obtained through untargeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis of samples from each human habitat and from the people that occupy those habitats. Mapping MS-derived data onto 3D models of the environments showed that frequently touched surfaces, such as handles (e.g., door, bicycle), resemble the molecular fingerprint of the human skin more closely than other surfaces that are less frequently in direct contact with humans (e.g., wall, bicycle frame). Approximately 50% of the MS/MS spectra detected were shared between people and the environment. Personal care products, plasticizers, cleaning supplies, food, food additives, and even medications that were found to be a part of the human habitat. The annotations indicate that significant transfer of chemicals takes place between us and our built environment. The workflows applied here will lay the foundation for future studies of molecular distributions in medical, forensic, architectural, space exploration, and environmental applications