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Fogacin, a novel cyclic octaketide produced by Streptomyces strain Tu 6319
No full textA new octaketide named fogacin (1) was isolated from Streptomyces sp. (strain T 6319). Furthermore two shunt metabolites, SEK4b (2) and anhydroSEK4b (3), were detected and identified as nonenzymatically cyclized products of polyketide intermediates built during the biosynthesis of actinorhodin. SEK4b (2) as well as anhydroSEK4b (3) were previously described as metabolites of genetically engineered strains
Taxonomy, fermentation, biological activities, isolation and characterization of metabolites obtained from a new strain of Streptomyces noursei (KC46)
No full textAn isolate, KC46 active against clinical resistant strains was isolated from Indian soil. Based on morphological features and biochemical characteristics it was identified as Streptomyces noursei. The active compounds isolated from KC46 using various fermentation methods (fermentation in shake flasks, in P-flasks, and also in a fermenter, using starch casein nitrate medium containing zinc sulphate) were characterized based on spectral data. The sulfur rich peptide, nosiheptide and related antibiotics were identified. Nosiheptide has been reported for the first time from a strain of S. noursei.Goettingen University, German
Taxonomy, fermentation, biological activities, isolation and characterization of metabolites obtained from a new strain of Streptomyces noursei (KC46)
No full textAn isolate, KC46 active against clinical resistant strains was isolated from Indian soil. Based on morphological features and biochemical characteristics it was identified as Streptomyces noursei. The active compounds isolated from KC46 using various fermentation methods (fermentation in shake flasks, in P-flasks, and also in a fermenter, using starch casein nitrate medium containing zinc sulphate) were characterized based on spectral data. The sulfur rich peptide, nosiheptide and related antibiotics were identified. Nosiheptide has been reported for the first time from a strain of S. noursei.Goettingen University, German
Synthesis and Precursor‐Directed Biosynthesis of New Hormaomycin Analogues
No full textSeveral new analogues of hormaomycin (1), a peptide lactone with interesting biological activities, were prepared by total synthesis or by precursor-directed biosynthesis. The new analogues 2a-c, 3a-c, O-MOM-1 and epi-O-MOM-1 as well as the model acyl tripeptides 20a-c and 21a-e were tested for their antibiotic activities to give new insights into structure-activity relationships of this class of compounds. In this context, an unexpected activity of 2c against C. albicans was discovered. The precursors necessary for feeding experiments, the amino acids 14a, 14b and 17, were prepared in 31, 48 and 55% yield over 4 and 3 steps, respectively. In addition, these studies provided some new information about the biosynthetic route to furnish compound 1. They also support the notion that the combination of chemical and biological methods may provide a broad range of analogues of an interesting biologically active natural product, (c) Wiley-VCH Verlag GmbH & Co
Biosynthetic Capacities of Actinomycetes. Part 36. Fogacin (I), a Novel Cyclic Octaketide Produced by Streptomyces Strain T 6319.
No full textInsights into the Biosynthesis of Hormaomycin, An Exceptionally Complex Bacterial Signaling Metabolite
No full textSummaryHormaomycin 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. In this study, we shed light on hormaomycin biosynthesis by a combination of feeding studies, isolation of the biosynthetic nonribosomal peptide synthetase (NRPS) gene cluster, and in vivo and in vitro functional analysis of enzymes. In addition, several nonnatural hormaomycin congeners were generated by feeding-induced metabolic rerouting. The NRPS contains numerous highly repetitive regions that suggest an evolutionary scenario for this unusual bacterial hormone, providing new opportunities for evolution-inspired metabolic engineering of novel nonribosomal peptides
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Studies towards the biosynthesis of the antiparasitic agents hormaomycin and borrelidin and structure elucidation of secondary metabolites from actinomycetes
No full textIm Mittelpunkt der Dissertation stehen Untersuchungen der Naturstoffe Hormaomycin und Borrelidin, zudem werden die Isolierung und Strukturaufklärung von Sekundärmetaboliten aus Actinomyceten durch chemisches und HPLC-DAD-Screening beschrieben.Die Vorläufer-dirigierte Biosynthese mit Hilfe des Produzenten des Peptidlactons Hormaomycin führt zu 17 neuen Derivaten des Naturstoffs mit Variationen in unterschiedlichen Molekülabschnitten, weiterhin kann die Produktion des Naturstoffs durch Fütterung von 2-Pyrrolcarbonsäure um bis zu 300 % gesteigert werden. Durch die gewonnenen Derivate sind neue Aussagen zur Biosynthese der ungewöhnlichen 3-(2'-Nitrocyclopropyl)alanin-Einheiten möglich, weiterhin werden Untersuchungen zum NRPS-Gencluster vorgestellt. Die neuen Analoga zeigen gegen P. falciparum und L. donovanii Aktivitäten im nanomolaren Bereich bei geringer Cytotoxizität. Struktur-Wirkungsbeziehungen lassen sich ableiten. Hormaomycin D2 hemmt als einziges Derivat das Wachstum von C. albicans. Die Gewinnung hochreinen Hormaomycins erlaubt Bestimmungen der stark lösungsmittelabhängigen Konformation des Peptidlactons durch NMR-Messungen sowie die Kristallisation für eine Röntgenstruktur.Im Rahmen der Screeningansätze konnten aus zwei marinen sowie zwei terrestrischen Actinomyceten insgesamt 11 Sekundärmetaboliten isoliert werden, von denen nur das Fogacin neu war. SEK4b und anhydroSEK4b wurden erstmals aus Wildstämmen isoliert.Die von Leadlay et al. postulierte Biosynthese des Borrelidins kann durch Fütterungsexperimente mit isotopenmarkierten Substanzen für den Makrolidring bestätigt werden, der Mechanismus für die Bildung der trans-(1R,2R)-Cyclopentandicarbonsäure hingegen erweist sich als falsch oder unvollständig.The core of the present thesis deals with studies of the natural products hormaomycin and borrelidin. Furthermore the isolation and structure elucidation of secondary metabolites from actinomycetes via chemical and HPLC-DAD screening is described.Precursor directed biosynthesis with the producer of the peptide lactone hormaomycin leads to the production of 17 new hormaomycin derivatives with variations in different parts of the molecule. The yield of the natural product can be increased up to 300 % by feeding of 2-pyrrolecarboxylic acid. These results provide new insight into the formation of the unique 3-(2'-nitrocyclopropyl)alanine building blocks, furthermore biosynthetic studies of the NRPS gene cluster are presented. All new analogues show remarkable activities against P. falciparum and L. donovanii in nanomolar range by concomitant low cytotoxicity. Structure-activity relationships are derived. Hormaomycin D2 is inhibiting the growth of C. albicans, no antimycotic acitivity is observed for any other derivative. NMR measurements and crystallisation for an X-ray structure are possible with highly pure hormaomycin and show highly solvent dependent conformations of the peptide lactone.The screening approaches lead to the isolation of 11 substances from actinomycetes of marine and terrestrial origin. Hereof, the polyketide fogacin is the only new metabolite. Besides, SEK4b and anhydroSEK4b are isolated from a wild type strain for the first time.The biosynthesis of borrelidin postulated by Leadlay and coworkers is confirmed for the ring structure via feeding experiments with 13C-labelled precursors. On the other hand, the mechanism for trans-cyclopentane-(1R,2R)-dicarboxylic acid formation appears to be wrong or at least incomplete
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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