Phocoenamicins B and C, New Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp (original) (raw)
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Antimicrobial Spirotetronate Metabolites from Marine-Derived Micromonospora harpali SCSIO GJ089
Journal of Natural Products, 2017
Two new spirotetronate aglycones, 22-dehydroxymethyl-kijanolide (1) and 8-hydroxy-22-dehydroxymethyl-kijanolide (2), along with seven new spirotetronate glycosides, microsporanates A−F (3−8) and tetrocarcin P (9), together with three known tetrocarcins [tetrocarcins A (10), B (11), and AC6H (12)], were isolated from fermentation broths of the marine-derived Micromonospora harpali SCSIO GJ089. The structures of 1−9 were elucidated on the basis of 1D and 2D NMR and MS spectroscopic data. Compounds 3− 8 feature an α,β-unsaturated carbonyl moiety within their spirotetronate skeletons. Moreover, compounds 3−12 displayed strong to moderate antibacterial activities against Gram positive bacteria Bacillus thuringiensis BT01 and B. subtilis BS01 with MIC values ranging from 0.016 to 8.0 μg/mL.
Marine Drugs
Antimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compounds displaying different antibiotic activities. Three marine Micromonospora strains (CA-214671, CA-214658 and CA-218877), identified as phocoenamicins producers, were chosen to scale up their production and LC/HRMS analyses proved that EtOAc extracts from their culture broths produce several structurally related compounds not disclosed before. Herein, we report the production, isolation and structural elucidation of two new phocoenamicins, phocoenamicins D and E (1–2), along with the known phocoenamicin, phocoenamicins B and C (3–5), as well as maklamicin (7) and maklamicin B (6), the latter being reported for the first time as a natural product. All the isolated compounds were tested aga...
Antibacterial Spirotetronate Polyketides from an Actinomadura sp. Strain A30804
Molecules
Large scale cultivation and chemical investigation of an extract obtained from Actimonadura sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C–G; 7–12), along with six known congeners, namely decatromicins A–B (1–2), BE-45722B–D (3–5), and pyrrolosporin A (6). The chemical structures of compounds 1–12 were characterized via comparison with previously reported data and analysis of 1D/2D NMR and MS data. The structures of all new compounds were highly related to the spirotetronate type compounds, decatromicin and pyrrolosporin, with variations in the substituents on the pyrrole and aglycone moieties. All compounds were evaluated for antibacterial activity against the Gram-negative bacteria, Acinetobacter baumannii and Gram-positive bacteria, Staphylococcus aureus and were investigated for their cytotoxicity against the human cancer cell line A549. Of these, decatromicin B (2), BE-45722B (3), and pyrrolosporin B (7) exh...
2016
Appadurai Muthamil Iniyan, Francisjoseph Rosemary Sharmila Joseph, Rajaretinam Rajesh Kannan, Samuel Gnana Prakash Vincent * 1 International Centre for Nanobiotechnology (ICN), Centre for Marine Science and Technology (CMST), Manonmaniam Sundaranar University, Rajakkamangalam, Kanyakumari Dist-629502, TN, India. 2 Molecular and Nanomedicine Research Unit, Centre for NanoScience and NanoTechnology (CNSNT), Sathyabama University, Jeppiaar Nagar, Rajiv Gandhi Road, Chennai-600119, TN, India.
Spirotetronate polyketides as leads in drug discovery
Journal of natural products, 2015
The discovery of chlorothricin (1) defined a new family of microbial metabolites with potent antitumor antibiotic properties collectively referred to as spirotetronate polyketides. These microbial metabolites are structurally distinguished by the presence of a spirotetronate motif embedded within a macrocyclic core. Glycosylation at the periphery of this core contributes to the structural complexity and bioactivity of this motif. The spirotetronate family displays impressive chemical structures, potent bioactivities, and significant pharmacological potential. This review groups the family members based on structural and biosynthetic considerations and summarizes synthetic and biological studies that aim to elucidate their mode of action and explore their pharmacological potential.
Exploring Micromonospora as Phocoenamicins Producers
Marine Drugs
Over the past few years, new technological and scientific advances have reinforced the field of natural product discovery. The spirotetronate class of natural products has recently grown with the discovery of phocoenamicins, natural actinomycete derived compounds that possess different antibiotic activities. Exploring the MEDINA’s strain collection, 27 actinomycete strains, including three marine-derived and 24 terrestrial strains, were identified as possible phocoenamicins producers and their taxonomic identification by 16S rDNA sequencing showed that they all belong to the Micromonospora genus. Using an OSMAC approach, all the strains were cultivated in 10 different media each, resulting in 270 fermentations, whose extracts were analyzed by LC-HRMS and subjected to High-throughput screening (HTS) against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. The combination of LC-UV-HRMS analyses, metabolomics analysis and mol...
Journal of Applied Microbiology, 2016
Aims: The aim of this study was to isolate and characterize the bioactive compound of Micromonospora auratinigra, HK-10 and its antibacterial inhibitory mechanism. Methods and Results: An oily bioactive compound was extracted from HK-10 (GenBank accession no. JN381554) and found to have promising antibacterial activity. The compound was characterized as 2-methylheptylisonicotinate (1) by 1 H, 13 C NMR and mass spectroscopy. Minimum inhibitory concentration (MIC) of this molecule was tested by micro broth dilution method and was found to be 70, 40, 80, 60, 60 and 50 lg for Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Echerichia coli, Pseudomonas aeruginosa and Mycobacterium abscessus respectively. The effects of compound 1 were studied on bacterial membrane structure using scanning electron microscopy. The results indicated a membrane-disrupting mechanism, resulting in the dysfunction of the cytoplasmic membrane structure and cell death of the pathogenic bacterial strains. Kinetics of growth of the test organisms was also analysed and indicated 2-methylheptylisonicotinate 1 as a bactericidal agent. Furthermore, we have studied the binding affinity of 1 towards different membrane proteins of pathogenic bacteria by in silico analysis. Conclusions: 2-methylheptylisonicotinate was isolated from M. auratinigra, a rare actinobacterial strain possessing antibacterial activity through a membrane-disrupting mechanism, and has MICs similar to standard antibiotic neomycin sulphate. It is the first report about a strain of M. auratinigra, isolated from Indo-Burma biodiversity hotspot of Northeast India with new antimicrobial activities. In silico studies have also supported these results performed on various membrane targets of pathogenic bacteria. Significance and Impact of the Study: The antibacterial potential of M. auratinigra is reported for the first time. The results indicate the possible use of 2-methylheptylisonicotinate as a source of antibacterial agent against dreaded human pathogens.
The Journal of Antibiotics, 2011
Two new 6,6-spiroacetal polyketides, spirotoamides A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces griseochromogenes JC82-1223 by screening of structurally unique compounds based on a search of spectral database. The fraction library was constructed using a systematic separation method to efficiently discover new metabolites from microbial sources such as actinomycetes and fungi. The structures of 1 and 2 were elucidated by 2D-NMR and mass spectrometric measurements. They belong to a class of polyketides, and contain a 6,6-spiroacetal core structure and a carboxamide group. The biosynthetic pathway of 1 and 2 is discussed in the text.
2013
Abstract: Polyketide 13 [=2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2propylchroman-4-one] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp. Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation. Due to tautomeric equilibrium, 13 in CD3OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI-MS/MS analysis. The 2-hydroxy-γ-pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4-hydroxy-α-pyrone and 2-hydroxy-γ-pyrone forms. During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin-resistant S. aureus (MRSA, ...
Secondary metabolites produced by marine actinomycete Micromonospora sp. A258
Vietnam Journal of Chemistry
In the course of our screening program, the EtOAc extract of Micromonospora sp. A258 from the sponge Haliclona oculata exhibited antimicrobial activity against both gram positive S.aureus ATCC25923 and gram-negative E.coli ATCC25922, S.enterica ATCC13076. This paper reports the isolation and structural elucidation of eight secondary metabolites including bacilsubteramide A (1), 4,9-dihydroxy-3-isobutyl-2,3,4,5-tetrahydrobenzo-azepin-1-one (2), indole-3-carboxylic acid (3), N-acetyltryptamine (4), N-(4-hydroxyphenyl)ethyl-methylbutanamide) (5), N-phenylacetamide (6), 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (7), (2R,3S)-butane-2,3-diol (8) from the culture broth of Micromonospora sp. A258. Their structures were determined by spectroscopic analysis including MS, 1D NMR and 2D NMR, as well as comparison with literature data.