Actinomycete bacteria produce a wide variety of secondary metabolites with diverse biological activities, some of which have been developed for human medicine. Rare actinomycetes are promising sources in search for new drugs, and their potential for producing biologically active molecules is poorly studied. In this work, we have investigated the diversity of actinomycetes in the shallow water sediments of the Trondheim fjord (Norway). Due to the use of different selective isolation methods, an unexpected variety of actinomycete genera was isolated. Although the predominant genera were clearly Streptomyces and Micromonospora, representatives of Actinocorallia, Actinomadura, Knoellia, Glycomyces, Nocardia, Nocardiopsis, Nonomuraea, Pseudonocardia, Rhodococcus and Streptosporangium genera were isolated as well. To our knowledge, this is the first report describing isolation of Knoellia and Glycomyces species from the marine environment. 35 selected actinomycete isolates were characterized by 16S rDNA sequencing, and were shown to represent strains from 11 different genera. In addition, these isolates were tested for antimicrobial activity and the presence of polyketide synthase and non-ribosomal peptide synthetase genes. This study confirms the significant biodiversity of actinobacteria in the Norwegian marine habitats, and their potential for producing biologically active compounds.
Marine actinobacteria are drawing more and more attention as a promising source of new natural products. Here we report isolation, genome sequencing and metabolic profiling of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics profiling of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family – lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural products, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites.
Twenty-three new derivatives of the heptaene nystatin analogue 28,29-didehydronystatin A(1) (1) (S44HP) were obtained by chemical modification of C16 carboxyl and amino groups of mycosamine. These derivatives comprised 15 carboxamides, 4 N-alkyl derivatives, 3 N-derivatives containing additional N-linked monosaccharide or disaccharide moiety (products of Amadori rearrangement), and 1 N-aminoacyl derivative. The derivatives have been tested in vitro against yeasts Candida albicans, Cryptococcus humicolus, and filamentous fungi (molds) Aspergillus niger and Fusarum oxysporum, as well as for hemolytic activity against human erythrocytes. Structure-activity relationships for the compounds obtained are discussed. The most active and least hemolytic derivative 3-(N,N-dimethylamino)propylamide of S44HP (6) was tested for acute toxicity and antifungal activity in animal model. Whereas amphotericin B and S44HP were active in vivo at doses close to the maximal tolerated dose, 6 was considerably less toxic and more active compared to these two antibiotics.
The cell-wall teichoic acids of Nocardiopsis dassonvillei IMRU 509T, IMRU 504 and IMRU 1250 and Nocardiopsis antarcticus VKM Ac-836T have the same unique structure that has not heretofore been found in bacteria. The polymer is built of 10 to 13 repeating units: -1snGro3-P-3-beta-D-GalNAc1-2snGro3-P-. The structure has been established by chemical analysis and with NMR spectroscopy. A study of the cell-wall monosaccharide composition, peptidoglycan, and cell phospholipids also provides evidence for the close similarity of these two species.
The study of an archived sample of crystallomycin complex using HPLC, ESI HRMS, and 2D NMR showed that two major components of the antibiotic, compounds and, are lipopeptides having the same peptide core, Asp1-cyclo(Dab2-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-), -acylated either with Δ-iso-tetradecenoyl or Δ-anteiso-pentadecenoyl that are identical to aspartocins C and B, respectively. According to the 2D NMR study, compound in DMSO solution exists as a mixture of four conformers. The producing strain was identified as. Compounds and have considerable Ca-dependent activity against Gram-positive bacteria including five MRSA strains.
Because of the spread of drug resistance, it is necessary to look for new antibiotics that are effective against pathogenic microorganisms. The purpose of this study was to analyse the species composition of actinobacteria isolated from the digestive tract of the millipedes Nedyopus dawydoffiae and to determine their antimicrobial properties. Species identification was carried out on the basis of the morphological and culture properties and the sequence of the 16S rRNA gene. Actinobacteria were grown in different liquid media. Antibiotic properties were determined against some Gram-positive and Gram-negative bacteria as well as fungi. Of the 15 isolated strains, 13 have antibiotic activity against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus—MRSA) and fungi, but there was no antibiotic activity against Gram-negative test strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. It was established that antibiotic-producing actinobacteria belong to eight species of the genus Streptomyces. Depending on the nutrient medium, actinobacteria demonstrate different antimicrobial activities. As an example, S. hydrogenans shows that even strains selected in one population differ by the range of antimicrobial activity and the level of biosynthesis. Since the antibiotic production is considered as a feature for species competition in the microbiota community, the variability of antibiotic production among different strains of the same species is an adaptive characteristic for the competition in millipedes’ digestive tract community.
The antibiotic INA 2770 active against methicillin resistant staphylococcus aureus (MRSA) was biotechnologically produced and isolated. This antibiotic is identical to cineromycin B. The characteristic features of the 1 H and 13 C NMR spectra of this compound were studied for the first time, and the conformational analysis was carried out by computational methods (molecular mechanics (MM3) force field) and using nuclear Overhauser effect experiments.
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