Come to the fore: The novel myxobacterial metabolite myxoprincomide is easy overlook in complex LC-MS data recorded for metabolome of Myxococcus xanthus DK1622, such that advanced analytical techniques were needed its discovery. By enhancing genomics-based natural products research with powerful tools in-depth mining, two additional "hidden" metabolites have been uncovered. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed,...

Releasing the cytopath: We have identified an N-myristoyl-D-asparagine (1) as free N-terminal prodrug scaffold in cytopathogenic Escherichia coli strains expressing colibactin gene cluster. Colibactin is released vivo upon cleavage of precolibactin. provide for first time evidence prodrug-like release mechanism colibactin. As a service to our authors and readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may be re-organized online...

Four new cyclic depsipeptides termed mirabamides A–D (1–4) have been isolated from the marine sponge Siliquariaspongia mirabilis and shown to potently inhibit HIV-1 fusion. Their structures were elucidated by NMR ESIMS, absolute stereochemistry of amino acids was determined using advanced Marfey's methods NMR. Mirabamides contain two entities, including 4-chlorohomoproline in 1–3 an unusual glycosylated acid, β-methoxytyrosine 4′-O-α-l-rhamnopyranoside (in 1, 2, 4), along with a rare...

Lepidium meyenii, known in South America as maca, has received attention worldwide a powerful energizer that improves physical and mental conditions increases fertility. Because of these reports, we investigated the secondary metabolites tuber maca. The methanol extract maca contained, addition to free sugars amino acids, following: uridine, malic acid its benzoyl derivative, glucosinolates, glucotropaeolin m-methoxyglucotropaeolin. glucosinolates their derived products have increasing due...

Six new depsipeptides belonging to two different structural classes, termed celebesides A−C and theopapuamides B−D, have been isolated from the marine sponge Siliquariaspongia mirabilis. Their structures were determined using extensive 2D NMR ESI-MS/MS techniques. Celebesides are unusual cyclic that comprise a polyketide moiety five amino acid residues, including an uncommon 3-carbamoyl threonine, phosphoserine residue in A B. Theopapuamides B−D undecapeptides with N-terminal fatty...

Eight new antimicrobial natural products named chrysophaentins A−H belonging to a structural class have been isolated from the marine chrysophyte alga Chrysophaeum taylori. Their structures were determined by extensive 2D NMR and MS techniques are characterized presence of two polyhalogenated, polyoxygenated ω,ω′-diarylbutene units connected ether bonds form suite macrocyclic products. Chrysophaentin A, most potent these antibiotics, inhibited growth clinically relevant Gram-positive...

Seven new depsipeptides, termed largamides A−G (1−7), and one cyclic peptide, largamide H (8), have been isolated from the marine cyanobacterium Oscillatoria sp. Their structures were determined by NMR ESI-MS techniques. The absolute configurations assigned using LC-MS, chiral HPLC, combined analysis of homonuclear heteronuclear 2,3J couplings, along with ROE data. Largamides, a single homogeneous cyanobacterial collection, represent three different structural classes peptides. Largamides...

Seven new antibacterials, motualevic acids A−F (1−6) and (4E)-(R)-antazirine (7), have been isolated from the marine sponge Siliquariaspongia sp. their structures elucidated by spectroscopic methods. Motualevic A−D are first glycyl conjugates of ω-brominated lipid (E)-14,14-dibromotetradeca-2,13-dienoic acid, acid F is long-chain 2H-azirine 2-carboxylic to be found in nature. Carboxylic acid-containing compounds 1 6 inhibit growth Staphylococcus aureus methicillin-resistant S. at 1.2−10.9 μg/mL.

Biosynthetic pathway intermediates related to genotoxin colibactin formation: a linear compound<bold>3</bold>bearing rare 7-methyl-4-azaspiro[2.4]hept-6-en-5-one residue.

Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are cyclic depsipeptides, whereas svetamycin E is linear analogue C. Their structures were determined using extensive spectroscopic analysis, their stereochemical configuration was established by combination NMR data, quantum mechanical calculations, chemical derivatizations. characterized the presence hydroxyl acetic acid five amino acids...

Symphytum officinale, commonly known as comfrey, constitutes a traditional medicinal plant with long-standing therapeutic history, and preparations thereof have been widely used for the treatment of painful muscle joint complaints, wound bone healing, inflammation. Today, its topical use is based on analgesic anti-inflammatory effects, which substantiated by modern clinical trials. However, molecular basis action remained elusive. Here, we show that hydroalcoholic extract comfrey root...

A new sulfated cyclic depsipeptide, termed mutremdamide A, and six highly N-methylated peptides, koshikamides C−H, were isolated from different deep-water specimens of Theonella swinhoei cupola. Their structures determined using extensive 2D NMR, ESI, or CDESI QTOF-MS/MS experiments absolute configurations established by quantum mechanical calculations, advanced Marfey's method, chiral HPLC. Mutremdamide displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid Nδ-carbamoyl-β-sulfated...

Aetheramides are structurally distinctive cyclic peptides isolated from a novel myxobacterial genus proposed to be termed "Aetherobacter". The structures were solved by combination of NMR analyses, quantum mechanical calculations, and chemical derivatizations. which contain unique polyketide moiety two amino acid residues potently inhibited HIV-1 infection with IC(50) values ~0.015 μM. Furthermore aetheramides showed cytostatic activity against human colon carcinoma (HCT-116) cells 0.11

Pseudomonas aeruginosa employs a characteristic pqs quorum sensing (QS) system that functions via the signal molecules PQS and its precursor HHQ. They control production of number virulence factors biofilm formation. Recently, we have shown sulfonamide substituted 2-benzamidobenzoic acids, which are known FabH inhibitors, also able to inhibit PqsD, enzyme catalyzing last key step in biosynthesis Here, describe further optimization characterization this class compounds as PqsD inhibitors....

The 18 kb "silent" luminmycin biosynthetic pathway from Photorhabdus luminescens was cloned into a vector by using the newly established linear–linear homologous recombination and successfully expressed in Escherichia coli. Luminmycins A–C (1–3) were isolated heterologous host, their structures elucidated 2D NMR spectroscopy HRESIMS. Luminmycin A is deoxy derivative of previously reported glidobactin A, while luminmycins B C most likely represent its acyclic intermediates. Compound 1 showed...

Three new siderophores, termed hyalachelins A–C (1–3), were isolated from the terrestrial myxobacterium Hyalangium minutum. Their structures determined by 2D NMR and HR-MS/MS experiments, their stereochemical configuration was established a combination of data, quantum mechanical calculations, circular dichroism experiments. Hyalachelins are unusual catecholate-type siderophores that bear 3,7,8-trihydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid. iron chelating activities...

Lepidium meyenii (Maca) is traditionally employed in the Andean region for its supposed properties improving fertility. The aim of this study was to determine effect subacute oral administration hexanic, methanolic and chloroformic extracts Maca root on sexual performance inexperienced male rats. following parameters were evaluated: 1st mount, intromission, ejaculation post-ejaculatory latencies, intercopulatory interval copulatory efficacy. All tested fractions significantly decreased...

The present work deals with the optimization of an inhibitor PqsD, enzyme essential for Pseudomonas aeruginosa quorum sensing apparatus. Molecular docking studies, supported by biophysical methods (surface plasmon resonance, isothermal titration calorimetry, saturation transfer difference NMR), were used to illuminate binding mode 5-aryl-ureidothiophene-2-carboxylic acids. Enabled make profound predictions, structure-based led increased inhibitory potency. Finally a covalent was obtained....

In our screening efforts to identify unique scaffolds from myxobacteria for the drug discovery process, we used LC-SPE-NMR-MS techniques isolate six linear peptides, termed macyranone A–F, Cystobacter fuscus MCy9118. The macyranones are characterized by a rare 2-methylmalonamide moiety and an α-amino ketone fragment including α′,β′-epoxyketone in A. Gene disruption experiments confirmed biosynthetic gene cluster of as PKS/NRPS hybrid. Detailed silico phylogenetic analysis unraveled that...

Continuing our investigations on plants belonging to the Asclepiadaceae family, three new cardenolide glycosides, 3'-O-β-d-glucopyranosylcalactin (1), 12-dehydroxyghalakinoside (2), and 6'-dehydroxyghalakinoside (3), along with known ghalakinoside (4) calactin (5), were isolated from roots of Pergularia tomentosa. The structures these compounds elucidated by extensive spectroscopic methods including 1D- 2D-NMR experiments as well ESIMS analysis. cardenolides caused apoptotic cell death...

The discovery, structure elucidation, and solid-phase synthesis of namalide, a marine natural product, are described. Namalide is cyclic tetrapeptide; its macrocycle formed by only three amino acids, with an exocyclic ureido phenylalanine moiety at C-terminus. absolute configuration namalide was established, analogs were generated through Fmoc-based solid phase peptide synthesis. We found that not containing l-Lys or l-allo-Ile inhibited carboxypeptidase A submicromolar concentrations. In...

ABSTRACT Cloning and engineering of natural product biosynthetic pathways followed by heterologous expression in a tractable host is widely used approach for genetic modification microbial secondary metabolites. Herein, we employed ccdB counterselection combined with oligonucleotide‐mediated recombineering to efficiently create point mutations complex nonribosomal peptide synthetase (NRPS) from Photorabdus luminescens directing the biosynthesis luminmides. After depth analysis luminmide...

Cystomanamides A–D were isolated as novel natural product scaffolds from Cystobacter fuscus MCy9118, and their structures established by spectroscopic techniques including 2D NMR, LC-SPE-NMR/-MS, HR-MS. The cystomanamides contain β-hydroxy amino acids along with 3-amino-9-methyldecanoic acid that is N-glycosylated in cystomanamide C D. gene cluster for biosynthesis was identified disruption PKS/NRPS hybrid incorporating an iso-fatty starter unit a reductive amination step at the interface of...