New chlorinated nitro-pyrrole antibiotics, Pyrrolomycin A and B SE-2080 A and B.

Ezaki, Norio; Shomura, Takashi; Koyama, Masato; Niwa, Tomizo; Kojima, Mictuo; Inouye, Shigeharu; Itö, Tatsuo; Niida, Taro

doi:10.7164/antibiotics.34.1363

Cited by 49 publications

(24 citation statements)

References 3 publications

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“…6) are produced by the actinomycete Actinosporangium vitaminophilum. These compounds are active against not only fungi but also some Gram-negative and Gram-positive bacteria (45,46).…”

Section: Naturally Occurring Nitroaromatic Compoundsmentioning

confidence: 99%

Nitroaromatic Compounds, from Synthesis to Biodegradation

Parales

2010

Microbiol Mol Biol Rev

744

470

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SUMMARY Nitroaromatic compounds are relatively rare in nature and have been introduced into the environment mainly by human activities. This important class of industrial chemicals is widely used in the synthesis of many diverse products, including dyes, polymers, pesticides, and explosives. Unfortunately, their extensive use has led to environmental contamination of soil and groundwater. The nitro group, which provides chemical and functional diversity in these molecules, also contributes to the recalcitrance of these compounds to biodegradation. The electron-withdrawing nature of the nitro group, in concert with the stability of the benzene ring, makes nitroaromatic compounds resistant to oxidative degradation. Recalcitrance is further compounded by their acute toxicity, mutagenicity, and easy reduction into carcinogenic aromatic amines. Nitroaromatic compounds are hazardous to human health and are registered on the U.S. Environmental Protection Agency's list of priority pollutants for environmental remediation. Although the majority of these compounds are synthetic in nature, microorganisms in contaminated environments have rapidly adapted to their presence by evolving new biodegradation pathways that take advantage of them as sources of carbon, nitrogen, and energy. This review provides an overview of the synthesis of both man-made and biogenic nitroaromatic compounds, the bacteria that have been identified to grow on and completely mineralize nitroaromatic compounds, and the pathways that are present in these strains. The possible evolutionary origins of the newly evolved pathways are also discussed.

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“…6) are produced by the actinomycete Actinosporangium vitaminophilum. These compounds are active against not only fungi but also some Gram-negative and Gram-positive bacteria (45,46).…”

Section: Naturally Occurring Nitroaromatic Compoundsmentioning

confidence: 99%

Nitroaromatic Compounds, from Synthesis to Biodegradation

Parales

2010

Microbiol Mol Biol Rev

744

470

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“…The pyrrolomycins are a family of antibiotics with high halogen content that are produced by Actinosporangium and Streptomyces species (3,6,8,9,19,23,24,31,40). Representative examples of the pyrrolomycins include dioxapyrrolomycin and pyrrolomycins A to D (Fig, 1).…”

mentioning

confidence: 99%

Cloning and Characterization of the Pyrrolomycin Biosynthetic Gene Clusters from Actinosporangium vitaminophilum ATCC 31673 and Streptomyces sp. Strain UC 11065

Zhang

Parry

2007

Antimicrob Agents Chemother

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The pyrrolomycins are a family of polyketide antibiotics, some of which contain a nitro group. To gain insight into the nitration mechanism associated with the formation of these antibiotics, the pyrrolomycin biosynthetic gene cluster from Actinosporangium vitaminophilum was cloned. Sequencing of ca. 56 kb of A. vitaminophilum DNA revealed 35 open reading frames (ORFs). Sequence analysis revealed a clear relationship between some of these ORFs and the biosynthetic gene cluster for pyoluteorin, a structurally related antibiotic. Since a gene transfer system could not be devised for A. vitaminophilum, additional proof for the identity of the cloned gene cluster was sought by cloning the pyrrolomycin gene cluster from Streptomyces sp. strain UC 11065, a transformable pyrrolomycin producer. Sequencing of ca. 26 kb of UC 11065 DNA revealed the presence of 17 ORFs, 15 of which exhibit strong similarity to ORFs in the A. vitaminophilum cluster as well as a nearly identical organization. Single-crossover disruption of two genes in the UC 11065 cluster abolished pyrrolomycin production in both cases. These results confirm that the genetic locus cloned from UC 11065 is essential for pyrrolomycin production, and they also confirm that the highly similar locus in A. vitaminophilum encodes pyrrolomycin biosynthetic genes. Sequence analysis revealed that both clusters contain genes encoding the two components of an assimilatory nitrate reductase. This finding suggests that nitrite is required for the formation of the nitrated pyrrolomycins. However, sequence analysis did not provide additional insights into the nitration process, suggesting the operation of a novel nitration mechanism.

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“…The other natural pyrrolomycins were less toxic: pyrrolomycin A and B showed LD50 values of 21.2 and about 100 mg/kg, respectively, when administered i.p. to JCL-ICR mice [37]; pyrrolomycins C and D showed LD50 values of 50 mg/kg and 20 mg/kg, respectively [35].…”

Section: Antibacterial Activity Of Natural Pyrrolomycinsmentioning

confidence: 96%

“…Pyrrolomycins (PM) are polyhalogenated metabolites known for their potent antimicrobial properties [31], isolated from the fermentation broth of Actinosporangium and Streptomyces species [32][33][34][35][36][37]. The antibiotics of this family include pyrrolomycins A, B, C, D, E, G, H, I, J and dioxapyrrolomycin ( Figure 3).…”

Section: Natural Pyrrolomycinsmentioning

confidence: 99%

“…Pyrrolomycins (PM) are polyhalogenated metabolites known for their potent antimicrobial properties [31], isolated from the fermentation broth of Actinosporangium and Streptomyces species [32][33][34][35][36][37] Important structural features of the pyrrolomycins are: (i) their high halogenation degree, which is usually represented by chlorine substituents; and (ii) in some cases, the presence of a nitro group at the position 3 of the pyrrole ring. The antibacterial activity of these derivatives may be closely related to their halogen content, because it increases as the degree of halogenation [38,39].…”

Section: Natural Pyrrolomycinsmentioning

confidence: 99%

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Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

et al. 2015

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Abstract:The emergence of antibiotic resistance is currently considered one of the most important global health problem. The continuous onset of multidrug-resistant Gram-positive and Gram-negative bacterial strains limits the clinical efficacy of most of the marketed antibiotics. Therefore, there is an urgent need for new antibiotics. Pyrrolomycins are a class of biologically active compounds that exhibit a broad spectrum of biological activities, including antibacterial, antifungal, anthelmintic, antiproliferative, insecticidal, and acaricidal activities. In this review we focus on the antibacterial activity and antibiofilm activity of pyrrolomycins against Gram-positive and Gram-negative pathogens. Their efficacy, combined in some cases with a low toxicity, confers to these molecules a great potential for the development of new antimicrobial agents to face the antibiotic crisis.

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New chlorinated nitro-pyrrole antibiotics, Pyrrolomycin A and B SE-2080 A and B.

Cited by 49 publications

References 3 publications

Nitroaromatic Compounds, from Synthesis to Biodegradation

Nitroaromatic Compounds, from Synthesis to Biodegradation

Cloning and Characterization of the Pyrrolomycin Biosynthetic Gene Clusters from Actinosporangium vitaminophilum ATCC 31673 and Streptomyces sp. Strain UC 11065

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

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