Structure of the lipopeptide antibiotic tsushimycin.

The amphomycin derivative tsushimycin has been crystallized and its structure determined at 1.0 A resolution. The asymmetric unit contains 12 molecules and with 1300 independent atoms this structure is one of the largest solved using ab initio direct methods.

Crystal structures of cephaibols.

The crystal structures of the peptaibol antibiotics cephaibol A, cephaibol B and cephaibol C have been determined at ca. 0.9 A resolution.

Structure of the alpha-amylase inhibitor tendamistat at 0.93 A.

The crystal structure of the proteinaceous alpha-amylase inhibitor tendamistat has been determined at 100 K to a resolution of 0.93 A. The final R factor for all reflections with F > 4sigma(F) is 9.

Coniosetin, a novel tetramic acid antibiotic from Coniochaeta ellipsoidea DSM 13856.

The coprophilic ascomycete Coniochaeta ellipsoidea DSM 13856 forms the new antibiotic coniosetin (1) in surface cultures grown on a medium containing malt extract and oatmeal. The structure of the compound C25H35NO4, MW 413, was determined by 2D-NMR and mass spectrometric studies. Coniosetin belongs to the class of tetramic acids; it consists of a substituted aliphatic bicyclic ring system linked to a tetramic acid subunit through a carbonyl center.

Ustilipids, acylated beta-D-mannopyranosyl D-erythritols from Ustilago maydis and Geotrichum candidum.

Ustilago species produce an extracellular oil that shows activity in various pharmaceutical assays. We isolated several complexes of this heterogeneous glycolipid from cultures of Ustilago maydis DSM 11494 and Geotrichum candidum ST 002515, and determined the chemical structures of these new compounds, termed ustilipids, on the basis of NMR experiments, mass spectra, and fatty acid analyses. They all possess a 4-O-beta-D-mannopyranosyl D-erythritol basic framework, the configuration of which was confirmed, after initial solvolysis, by a single-crystal X-ray structure analysis.

Cyclipostins, novel hormone-sensitive lipase inhibitors from Streptomyces sp. DSM 13381. II. Isolation, structure elucidation and biological properties.

Hormone-sensitive lipase (HSL) is a key enzyme of lipid metabolism and its control is therefore a target in the treatment of diabetes mellitus. Cultures of the Streptomyces species DSM 13381 have been shown to potently inhibit HSL. Ten inhibitors of HSL, termed cyclipostins, have been isolated from the mycelium of this microorganism and a further nine related compounds detected.

Structures of glycopeptide antibiotics with peptides that model bacterial cell-wall precursors.

The vancomycin-related antibiotics balhimycin and degluco-balhimycin have been crystallized in complexes with di-, tri- and pentapeptides that emulate bacterial cell-wall precursors, and four structures determined at atomic resolution (<1 A). In addition to the features expected from previous structural and spectroscopic studies, two new motifs were observed that may prove important in the design of antibiotics modified to overcome bacterial resistance. A changed binding mode was found in two dipeptide complexes, and a new type of face-to-face oligomerization (in addition to the well-established back-to-back dimerization) was seen when the model peptide reaches a critical fraction of the size of the cell-wall precursor pentapeptide.

Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2.

The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone. The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide. The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro.

Pluraflavins, potent antitumor antibiotics from Saccharothrix sp. DSM 12931.

The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931. The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations. The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-gamma-pyrone ring system.

The chemical structure of mumbaistatin, a novel glucose-6-phosphate translocase inhibitor produced by Streptomyces sp. DSM 11641.

The characterization of the structure of mumbaistatin (1), an effective inhibitor of the glucose-6-phosphatase system (EC 3.1.3.

Cephaibols, new peptaibol antibiotics with anthelmintic properties from Acremonium tubakii DSM 12774.

Two groups of new peptaibol-type antibiotics termed cephaibols have been isolated from the fungus Acremonium tubakii, DSM 12774. These 16- or 17-unit straight-chain peptides, whose structures were characterized by amino acid analyses, 2-D NMR experiments, and by mass spectrometric sequencing, have a high content of the unusual amino acids aminoisobutyric acid and isovaline. The principal constituent of the novel peptaibol mixture is cephaibol A, which is formed in abundance in cultures of the wild strain.

Friulimicins: novel lipopeptide antibiotics with peptidoglycan synthesis inhibiting activity from Actinoplanes friuliensis sp. nov. II. Isolation and structural characterization.

Four novel lipopeptide antibiotics, friulimicins A, B, C, and D, were isolated from cultures of Actinoplanes friuliensis HAG 010964 after fermentation in different nutrient media. The new compounds were separated by ion-exchange chromatography from the acidic lipopeptides of the amphomycin type also present in the culture fluid, compounds A-1437 A, B, E, and G. The principal constituent friulimicin B, C59H94N14O19, was structurally characterized by mass spectrometric investigations of its hydrolysis and partial degradation products and by sequencing of the cyclic acyl peptide.

Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus thom DSM 11247. Isolation and structural elucidation.

Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and kodaistatin C, C35H34O12, molecular weight 646, have been isolated from cultures of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-exclusion chromatography, and various preparative HPLC steps. The use of a range of 2D NMR measurements, in particular 13C-13C correlation measurements, has led to the clarification of the structure of kodaistatin A. Kodaistatin C is a hydroxylated derivative of kodaistatin A.

Ala(0)-actagardine, a new lantibiotic from cultures of Actinoplanes liguriae ATCC 31048.

The actagardine-producing strain Actinoplanes liguriae ATCC 31048, forms an additional lantibiotic when it is cultured on mannitol and soya meal. The new compound, Ala(0)-actagardine (1), has been isolated by solid-phase extraction followed by a two-step chromatographic separation. The molecular formula of 1 is C84H129N21O25S4.

Feglymycin, a novel inhibitor of the replication of the human immunodeficiency virus. Fermentation, isolation and structure elucidation.

The novel peptide feglymycin has been isolated from cultures of Streptomyces sp. DSM 11171 by solid phase extraction, size exclusion chromatography and repeated reversed-phase chromatography. The molecular weight was found to be 1900.

3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874.

New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were obtained as yellow powders after sequential purification by chromatography on MCI Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography.

Structure of balhimycin and its complex with solvent molecules.

Balhimycin is a naturally occurring glycopeptide antibiotic, related to vancomycin which acts by binding nascent bacterial cell-wall peptide ending in the sequence D-Ala-D-Ala. Crystals of balhimycin are monoclinic, space group P21, a = 20.48 (10), b = 43.

Three-dimensional structure of moenomycin A--a potent inhibitor of penicillin-binding protein 1b.

The first three-dimensional structure of moenomycin A in aqueous solution based on NMR-derived distance constraints and molecular dynamics simulations is presented. The antibiotic moenomycin A was obtained from the FlavomycinR complex by ultrafiltration, chromatography on a DEAE-cellulose ion exchanger and reverse-phase chromatography in 98% purity. In contrast to the previously reported behaviour, the compound gave rise to well-resolved NMR spectra in standard solvents.

Carbohydrate and protein-based inhibitors of porcine pancreatic alpha-amylase: structure analysis and comparison of their binding characteristics.

The crystal structures of porcine pancreatic alpha-amylase isozyme II (PPA II) in its free form and complexed with the trestatin A derived pseudo-octasaccharide V-1532 have been determined using Patterson search techniques at resolutions of 2.3 and 2.2 angstroms, respectively.

Complete 1H nuclear magnetic resonance assignments and structural characterization of a fusion protein of the alpha-amylase inhibitor tendamistat with the activation domain of the human immunodeficiency virus type 1 Tat protein.

Complete sequence-specific assignments of the 1H-NMR spectrum of a fusion protein of the alpha-amylase inhibitor tendamistat from Streptomyces tendae and the activation domain of Tat from human immunodeficiency virus type 1 (HIV-1) was obtained by homonuclear two-dimensional NMR methods. The protein behaves as expected for an ideal fusion protein: the flexible linker allows an almost completely decoupled motion of the subunits of the protein and the two subunits show almost no mutual interaction. In the tendamistat part, small structural distortions due to exchange of the carboxy-terminal leucine propagate mainly via the hydrogen bonds of the beta-sheet and the disulfide bond.