Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

Kevin, Dion A.; Meujo, Damaris A. F.; Hamann, Mark T.

doi:10.1517/17460440802661443

Cited by 166 publications

(153 citation statements)

References 157 publications

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“…In the 2D-ROESY spectrum, the correlations of the C-4-methoxy group with H-5, the C-6-methoxy group with H-4, and the coupling constant of H4 and H5 (J 4,5 ϭ 11.4) revealed that the C-4-methoxy group and H-5 were on one side of ring A, while the C-6-methoxy group and H-4 were on the opposite side. The ROE correlation of the C-16-methoxy group with H-17, H-17 with the C-20-methoxy group, and the C-20-methoxy group with H-21 revealed that they were on the same side of rings C, D, and E. Although 1 H-and 13 C-NMR data of C-25 were not identical to those of etheromycin, the coupling constants (J 24,25 and J 25,26 ) were similar to those of etheromycin, and a careful analysis of 2D-ROESY signals of ring F revealed that 1.264-B and etheromycin shared identical relative configurations of ring F. The coupling constants of H-4Ј and H-5Ј(J 4Ј,5Ј ϭ 9.0 or 10.8) of ring G inferred that they were on opposite sides of the ring, like etheromycin. Due to the existence of the C-8-methoxy group, the configuration of ring A of 1.264-B should be the same as that of etheromycin (40).…”

Section: Resultsmentioning

confidence: 92%

“…1) are a unique class of type I polyketides with a high degree of promise for the control of drug-resistant bacteria and parasites, and they have been widely used as effective veterinary drugs and food additives in animal husbandry (13). These molecules also show a broad spectrum of bioactivity, including antifungal, antiviral, antitumor, herbicidal, and anti-inflammatory activity, as well as effects on the central nervous system (CNS) and immunoregulatory systems (24). The ability of polyethers to transport cations across plasma membranes leads to depolarization and succedent cell death.…”

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confidence: 99%

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Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes

Wang

Ning

et al. 2011

Appl Environ Microbiol

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Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes.Programs aimed at the discovery of new secondary metabolites with interesting biological activities from microbial sources have found an impressive number of compounds during the past 50 years. Actinomycetes represent one of the most prolific microbial sources for the discovery of bioactive metabolites (5, 6), many of which are produced by polyketide synthase (PKS) systems (6, 42). Polyether ionophores (Fig.

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Section: Resultsmentioning

confidence: 92%

mentioning

confidence: 99%

Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes

Wang

Ning

et al. 2011

Appl Environ Microbiol

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“…The ability of polyether ionophores to control drug-resistant bacteria and parasitic infections is well known, but these compounds also show a broad spectrum of bioactivities, including antifungal, antiviral, antitumor, herbicidal, and anti-inflammatory activities (58,59). In this study, a relatively high number of polyether-producing actinomycetes were isolated, notably the acidophilic streptomycetes (Streptomyces sp.…”

Section: Discussionmentioning

confidence: 97%

Red Soils Harbor Diverse Culturable Actinomycetes That Are Promising Sources of Novel Secondary Metabolites

Guo

Ning

et al. 2015

Appl Environ Microbiol

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Red soils, which are widely distributed in tropical and subtropical regions of southern China, are characterized by low organic carbon, high content of iron oxides, and acidity and, hence, are likely to be ideal habitats for acidophilic actinomycetes. However, the diversity and biosynthetic potential of actinomycetes in such habitats are underexplored. Here, a total of 600 actinomycete strains were isolated from red soils collected in Jiangxi Province in southeast China. 16S rRNA gene sequence analysis revealed a high diversity of the isolates, which were distributed into 26 genera, 10 families, and 7 orders within the class Actinobacteria; these taxa contained at least 49 phylotypes that are likely to represent new species within 15 genera. The isolates showed good physiological potentials for biosynthesis and biocontrol. Chemical screening of 107 semirandomly selected isolates spanning 20 genera revealed the presence of at least 193 secondary metabolites from 52 isolates, of which 125 compounds from 39 isolates of 12 genera were putatively novel. Macrolides, polyethers, diketopiperazines, and siderophores accounted for most of the known compounds. The structures of six novel compounds were elucidated, two of which had a unique skeleton and represented characteristic secondary metabolites of a putative novel Streptomyces phylotype. These results demonstrate that red soils are rich reservoirs for diverse culturable actinomycetes, notably members of the families Streptomycetaceae, Pseudonocardiaceae, and Streptosporangiaceae, with the capacity to synthesize novel bioactive compounds. While high-throughput sequencing methods expand our understanding of species diversity in microbial communities and reveal the presence of many new groups that were previously undetected in cultivation studies, the availability of pure cultures is still essential in order to discover new or useful bioactive compounds from microorganisms. As the most prolific secondary metabolite producers, actinomycetes account for approximately 41% of the bioactive microbial metabolites that have been discovered (1). In recent years, with the emergence of antibiotic-resistant microbial pathogens and rediscovery of known bioactive compounds, special habitats in the ocean (2, 3), sponges (4), plants (5, 6), and insects (7) have been found to be potentially important in the search and discovery of bioactive compound-producing strains. Nevertheless, soil is still the predominant source of secondary metabolite-producing actinomycetes. Unexplored and underexplored soil habitats have been found to be a rich source of actinomycetes that produce novel bioactive metabolites (8-10). Acidic soils in China, mostly red soils, are one such habitat.Red soils are generated by abundant rainfall and high temperature and are widespread in tropical and subtropical regions of southern China, covering about 1.13 million km 2 (11). These soils have been subjected to intensive weathering, and mineral nutrients (including Ca, Mg, P, and K) in the soil are mostly eluted, form...

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“…We succeeded to crystallizethe aforementioned natural product in the form of its methanol solvate. Dianemycin belongs to the class of carboxyl ionophores that complex the first row metal cations and therefore affect the transport of these latter in mitochondria [2]. This property results in outstanding activity against chloroquine-resistant forms of malaria.…”

mentioning

confidence: 99%

Crystal structure of methanolsodium dianemycin — methanol (1:2), Na(C47H77O14)(CH4O) · 2CH4O

Kumpiņš¹,

Belyakov²,

Bizdēna³

et al. 2012

Zeitschrift Für Kristallographie - New Crystal Structures

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Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

Cited by 166 publications

References 157 publications

Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes

Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes

Red Soils Harbor Diverse Culturable Actinomycetes That Are Promising Sources of Novel Secondary Metabolites

Crystal structure of methanolsodium dianemycin — methanol (1:2), Na(C47H77O14)(CH4O) · 2CH4O

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