Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling .

Heterologous expression of an terpenoid gene cluster derived from Gö66 in J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (-), along with a known compound, labdanmycin A. Compounds - were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed.

The Structure of Cyclodecatriene Collinolactone, its Biosynthesis, and Semisynthetic Analogues: Effects of Monoastral Phenotype and Protection from Intracellular Oxidative Stress.

Recently described rhizolutin and collinolactone isolated from Streptomyces Gö 40/10 share the same novel carbon scaffold. Analyses by NMR and X-Ray crystallography verify the structure of collinolactone and propose a revision of rhizolutin's stereochemistry. Isotope-labeled precursor feeding shows that collinolactone is biosynthesized via type I polyketide synthase with Baeyer-Villiger oxidation.

First Evidence of Dehydroabietic Acid Production by a Marine Phototrophic Gammaproteobacterium, the Purple Sulfur Bacterium MT86.

The production of secondary metabolites by a new isolate of the purple sulfur bacterium , which had shown antibiotic activities during a preliminary study, revealed the production of several metabolites. Growth conditions suitable for the production of one of the compounds shown in the metabolite profile were established and compound was purified. The molecular formula of compound (CHO₂) was determined by high resolution mass spectra, and its chemical structure by means of spectroscopic methods.

Investigations into the biosynthesis of the antifungal strobilurins.

The strobilurins are important antifungal metabolites isolated from a number of basidiomycetes and have been valuable leads for the development of commercially important fungicides. Isotopic labelling studies with early and advanced intermediates confirm for the first time that they are produced via a linear tetraketide, primed with the rare benzoate starter unit, itself derived from phenylalanine via cinnamate. Isolation of a novel biphenyl metabolite, pseudostrobilurin B, provides evidence for the involvement of an epoxide in the key rearrangement to form the β-methoxyacrylate moiety essential for biological activity.

Structure and Biosynthesis of Isatropolones, Bioactive Amine-Scavenging Fluorescent Natural Products from Streptomyces Gö66.

The natural products isatropolone A-C (1-3) were reisolated from Streptomyces Gö66, with 1 and 3 showing potent activity against Leishmania donovani. They contain a rare tropolone ring derived from a type II polyketide biosynthesis pathway. Their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates.

Insights into the bioactivity of mensacarcin and epoxide formation by MsnO8.

Mensacarcin, a potential antitumour drug, is produced by Streptomyces bottropensis. The structure consists of a three-membered ring system with many oxygen atoms. Of vital importance in this context is an epoxy moiety in the side chain of mensacarcin.

Cloning and heterologous expression of three type II PKS gene clusters from Streptomyces bottropensis.

Mensacarcin is a potent cytotoxic agent isolated from Streptomyces bottropensis. It possesses a high content of oxygen atoms and two epoxide groups, and shows cytostatic and cytotoxic activity comparable to that of doxorubicin, a widely used drug for antitumor therapy. Another natural compound, rishirilide A, was also isolated from the fermentation broth of S.

Insights into the biosynthesis of hormaomycin, an exceptionally complex bacterial signaling metabolite.

Hormaomycin produced by Streptomyces griseoflavus is a structurally highly modified depsipeptide that contains several unique building blocks with cyclopropyl, nitro, and chlorine moieties. Within the genus Streptomyces, it acts as a bacterial hormone that induces morphological differentiation and the production of bioactive secondary metabolites. In addition, hormaomycin is an extremely potent narrow-spectrum antibiotic.

Phenalinolactones A-D, terpenoglycoside antibiotics from Streptomyces sp. Tü 6071.

Four new terpenoglycoside antibiotics, phenalinolactones A-D were isolated from Streptomyces sp. Tü 6071. The structures were elucidated on the basis of detailed NMR and MS analyses.

Production of a Blue Pigment (Glaukothalin) by Marine Rheinheimera spp.

Two gamma-Proteobacteria strains, that is, HP1 and HP9, which both produce a diffusible deep blue pigment, were isolated from the German Wadden Sea and from the Øresund, Denmark, respectively. Both strains affiliate with the genus Rheinheimera. Small amounts of the pigment could be extracted from HP1 grown in a 50 L fermenter and were purified chromatographically.

Structures of viscotoxins A1 and B2 from European mistletoe solved using native data alone.

Crystals of the cytotoxic thionin proteins viscotoxins A1 and B2 extracted from mistletoe diffracted to high resolution (1.25 and 1.05 A, respectively) and are excellent candidates for testing crystallographic methods.

A comparative analysis of the sugar phosphate cyclase superfamily involved in primary and secondary metabolism.

Sugar phosphate cyclases (SPCs) catalyze the cyclization of sugar phosphates to produce a variety of cyclitol intermediates that serve as the building blocks of many primary metabolites, for example, aromatic amino acids, and clinically relevant secondary metabolites, for example, aminocyclitol/aminoglycoside and ansamycin antibiotics. Feeding experiments with isotopically labeled cyclitols revealed that cetoniacytone A, a unique C(7)N-aminocyclitol antibiotic isolated from an insect endophytic Actinomyces sp., is derived from 2-epi-5-epi-valiolone, a product of SPC.

Actinomycins with altered threonine units in the beta-peptidolactone.

Five new members of the actinomycin family, actinomycins G2-G6 (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the alpha-ring of the novel compounds contains the unusual amino acid 3-hydroxy-5-methylproline, while the beta-ring includes N-methylalanine and either a chlorinated or hydroxylated threonine moiety.

Fogacin, a novel cyclic octaketide produced by Streptomyces strain Tü 6319.

A new octaketide named fogacin (1) was isolated from Streptomyces sp. (strain Tü 6319). Furthermore two shunt metabolites, SEK4b (2) and anhydroSEK4b (3), were detected and identified as non-enzymatically cyclized products of polyketide intermediates built during the biosynthesis of actinorhodin.

New aminophenoxazinones from a marine Halomonas sp.: fermentation, structure elucidation, and biological activity.

The addition of anthranilic acid to the culture medium of the marine derived Halomonas sp. strain GWS-BW-H8hM completely altered the secondary metabolite pattern relative to the standard conditions. The red-orange color of the culture filtrate extract was the result of the production of 2-aminophenoxazin-3-one (1), chandrananimycin C (5) and three new derivatives of 1 with a previously unknown substitution pattern: 2-amino-, 2-amino-8-benzoyl-, and 2-amino-8-(4-hydroxybenzoyl)-6-hydroxyphenoxazin-3-one (2-4).

Resistoflavine, cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7.

In our systematic screening programme for marine actinomycetes, a bioactive Streptomycete was isolated from marine sediment samples of Bay of Bengal, India. The taxonomic studies indicated that the isolate belongs to Streptomyces chibaensis and it was designated as S. chibaensis AUBN1/7.

Effect of the solvent on the conformation of a depsipeptide: NMR-derived solution structure of hormaomycin in DMSO from residual dipolar couplings in a novel DMSO-compatible alignment medium.

The macrocyclic compound hormaomycin has been investigated by NMR spectroscopy and by restrained molecular-dynamics simulations. Measurement of residual dipolar couplings induced by dissolving the depsipeptide in a polyacrylamide gel compatible with DMSO and their incorporation into the structure calculation of the title compound improved the precision of the family of structures. In DMSO the macrocyclic ring shows two beta-turns, whose positions in the sequence differ from those found in the CDCl3 solution structure and in the crystal structure obtained from hexylene glycol/H2O (50:50).

1-Hydroxy-1-norresistomycin, a new cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7.

In our systematic screening programme for marine actinomycetes, a bioactive streptomycete was isolated from marine sediment samples of the Bay of Bengal, India. The isolate yielded a new cytotoxic compound. This was obtained by solvent extraction followed by chromatographic purification.

Archazolid and apicularen: novel specific V-ATPase inhibitors.

Background: V-ATPases constitute a ubiquitous family of heteromultimeric, proton translocating proteins. According to their localization in a multitude of eukaryotic membranes, they energize many different transport processes. Since their malfunction is correlated with various diseases in humans, the elucidation of the properties of this enzyme for the development of selective inhibitors and drugs is one of the challenges in V-ATPase research.

Retymicin, galtamycin B, saquayamycin Z and ribofuranosyllumichrome, novel secondary metabolites from Micromonospora sp. Tü 6368. II. Structure elucidation.

A detailed screening of the secondary metabolite pattern from Micromonospora sp. strain Tü 6368 resulted in the isolation of ten compounds belonging to five different structural families. The structures of the novel compounds 1-(alpha-ribofuranosyl)-lumichrome (3), retymicin (7), galtamycin B (11) and saquayamycin Z (14) were assigned by spectroscopic methods and chemical transformations.

Retymicin, galtamycin B, saquayamycin Z and ribofuranosyllumichrome, novel secondary metabolites from Micromonospora sp. Tü 6368. I. Taxonomy, fermentation, isolation and biological activities.

A new xanthone compound named retymicin (1) was isolated together with galtamycin B (2) and saquayamycin Z (3), new members of the galtamycin and saquayamycin families, respectively, and the new lumichrome derivative 1-(alpha-ribofuranosyl)-lumichrome (4) from Micromonospora strain Tü 6368, isolated from a soil sample collected in Romania. Retymicin, galtamycin B and saquayamycin Z show cytostatic effects to various human tumor cell lines whereas saquayamycin Z is also active against Gram-positive bacteria.

Chinikomycins A and B: isolation, structure elucidation, and biological activity of novel antibiotics from a marine Streptomyces sp. isolate M045.

In our screening of marine Streptomycetes for bioactive principles, two novel antitumor antibiotics designated as chinikomycins A (2a) and B (2b) were isolated together with manumycin A (1), and their structures were elucidated by a detailed interpretation of their spectra. Chinikomycins A (2a) and B (2b) are chlorine-containing aromatized manumycin derivatives of the type 64-pABA-2 with an unusual para orientation of the side chains. They exhibited antitumor activity against different human cancer cell lines, but were inactive in antiviral, antimicrobial, and phytotoxicity tests.

The structure of hormaomycin and one of its all-peptide aza-analogues in solution: syntheses and biological activities of new hormaomycin analogues.

Four new aza-analogues of hormaomycin 1, a secondary metabolite with interesting biological activities produced by Streptomyces griseoflavus, were synthesized and subjected to preliminary tests of their antibiotic activity to provide new insights into the structure-activity relationship studies of this class of compounds. The solution structures of hormaomycin 1 and its aza-analogue 2 a were determined by NMR spectroscopy. The data exhibited a reasonably rigid conformation for both molecules, stabilized by stacking interactions between the aromatic moieties attached to the ring and the side chain.

Aspochalamins A-D and aspochalasin Z produced by the endosymbiotic Fungus Aspergillus niveus LU 9575. II. Structure elucidation.

The structures of new cytochalasan fungal metabolites aspochalamins A-D have been elucidated by ESI-FTICR-MS, NMR spectroscopy, and chiral amino acid analysis. Aspochalamins A-D consist of different aspochalasin skeletons connected at position C-19 to the N terminus of the tripeptidic moiety amide anthranoyl-L-alanine-E-didehydrotryptamide. Furthermore, the structure of a new aspochalasin analog, aspochalasin Z, was derived from its molecular mass and NMR data as 10-isopropyl-14-methyl[11]-cytochalasa-6Z,13E,19E-triene-1,21-dione.

Final elucidation of the absolute configuration of the signal metabolite hormaomycin.

The complete absolute configuration of hormaomycin 1 a has been established by HPLC and HPLC/MS experiments with appropriately derivatized 4-propylprolines, (2S,4S)-6 and (2R,4R)-6, as well as 4-(Z)-propenylprolines, cis-5 and trans-5, and also feeding experiments with enantiomerically pure samples of the deuterium-labeled 3-(2'-nitrocyclopropyl)alanine, (2S)-3,3-[D2]15 and (2S)-2,2'-[D2]15, and 4-(Z)-propenylproline 2',4-[D2]-(2S,4R)-5. The latter five amino acids were prepared for the first time and allowed one to unequivocally assign the hitherto unknown absolute configurations of the last four stereocenters in hormaomycin 1 a. As a bonus, some new information about the biosynthesis of this molecule has also been gathered.