Streptogramins – Two are better than one!

Mast, Yvonne; Wohlleben, Wolfgang

doi:10.1016/j.ijmm.2013.08.008

Cited by 94 publications

(78 citation statements)

References 64 publications

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“…But in this study we found that the activity of PapR6 binding to the snaF promoter was unaffected in the presence of both or either PI or PII. Nevertheless, given that the regulation of PapR6 in PII biosynthesis is possibly performed by affecting the formation of the intermediate C 11 ␣␤-unsaturated thioester as well as the supply of the precursor isobutyryl-CoA, it is likely that the DNA-binding activity of PapR6 is modulated by isobutyryl-CoA or the C 11 ␣␤-unsaturated thioester, but this remains to be determined. In addition, although no HK gene was found nearby, we still could not exclude the possibility that the activity of PapR6 is modulated by an HK.…”

Section: Discussionmentioning

confidence: 99%

“…During the past few years, many efforts have been made toward an understanding of the regulation of pristinamycin production. PapR1, PapR2, and PapR4, which show high amino acid sequence similarities to Streptomyces antibiotic regulatory proteins (SARPs) (e.g., ActII-ORF4 and RedD from Streptomyces coelicolor), have been identified as activators of both PI and PII biosynthesis, while PapR3 and PapR5, which belong to the TetR family of proteins, function as transcriptional repressors of PI and PII production (10,11). Nevertheless, the regulatory mechanisms underlying their functions and their interplay with each other (PapR1 to PapR5) still await elucidation.…”

mentioning

confidence: 99%

“…Two direct target genes, papR1 and spbR itself, have been determined; the precise SpbR-binding motif has been defined, revealing that its effect on pristinamycin biosynthesis might be mediated by the SARP family protein PapR1. To date, however, nothing is known about the role of PapR6, a possible member of bacterial two-component system response regulators (RRs) (10,11).…”

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confidence: 99%

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PapR6, a Putative Atypical Response Regulator, Functions as a Pathway-Specific Activator of Pristinamycin II Biosynthesis in Streptomyces pristinaespiralis

Dun¹,

Zhao²,

Zheng³

et al. 2014

J. Bacteriol.

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cThere are up to seven regulatory genes in the pristinamycin biosynthetic gene cluster of Streptomyces pristinaespiralis, which infers a complicated regulation mechanism for pristinamycin production. In this study, we revealed that PapR6, a putative atypical response regulator, acts as a pathway-specific activator of pristinamycin II (PII) biosynthesis. Deletion of the papR6 gene resulted in significantly reduced PII production, and its overexpression led to increased PII formation, compared to that of the parental strain HCCB 10218. However, either papR6 deletion or overexpression had very little effect on pristinamycin I (PI) biosynthesis. Electrophoretic mobility shift assays (EMSAs) demonstrated that PapR6 bound specifically to the upstream region of snaF, the first gene of the snaFE1E2GHIJK operon, which is likely responsible for providing the precursor isobutyryl-coenzyme A (isobutyryl-CoA) and the intermediate C 11 ␣␤-unsaturated thioester for PII biosynthesis. A signature PapR6-binding motif comprising two 4-nucleotide (nt) inverted repeat sequences (5=-GAGG-4 nt-CCTC-3=) was identified. Transcriptional analysis showed that inactivation of the papR6 gene led to markedly decreased expression of snaFE1E2GHIJK. Furthermore, we found that a mutant (snaFmu) with base substitutions in the identified PapR6-binding sequence in the genome exhibited the same phenotype as that of the ⌬papR6 strain. Therefore, it may be concluded that pathway-specific regulation of PapR6 in PII biosynthesis is possibly exerted via controlling the provision of isobutyryl-CoA as well as the intermediate C 11 ␣␤-unsaturated thioester. Streptomyces pristinaespiralis produces pristinamycin, which is a streptogramin-like antibiotic and a mixture of two structurally different components: pristinamycin I (PI), a branched cyclic hexadepsipeptide, and pristinamycin II (PII), a polyunsaturated cyclopeptide macrolactone (1). PI and PII are cosynthesized at a ratio of 30:70 and show strong synergistic activity. The combined application of both components yields an antibacterial activity up to 100 times higher than that of each single component (2). Pristinamycin is attracting more and more interest for its activity against many multiple-drug-resistant Gram-positive bacteria, such as methicillin-resistant staphylococci and vancomycin-resistant Enterococcus faecium (2).The gene cluster responsible for the biosynthesis of PI and PII has been well characterized for S. pristinaespiralis (3-9); all essential PI/PII biosynthetic genes are proposed to be included in a 210-kb "supercluster," in which the pristinamycin gene cluster is interspersed with a cryptic type II polyketide biosynthetic gene cluster (10). Interestingly, there are seven regulatory genes in the pristinamycin biosynthetic gene cluster, including papR1 to papR6 and spbR, which infers a complicated regulatory mechanism for pristinamycin production. It has long been suggested that manipulation of the regulatory network governing antibiotic biosynthesis in Streptomyces may represent an ef...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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PapR6, a Putative Atypical Response Regulator, Functions as a Pathway-Specific Activator of Pristinamycin II Biosynthesis in Streptomyces pristinaespiralis

Dun¹,

Zhao²,

Zheng³

et al. 2014

J. Bacteriol.

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“…Streptogramin antibiotics are a unique class of antibacterials consisting of two groups of structurally unrelated molecules: group A streptogramins (polyunsaturated macrolactones) and group B streptogramins (cyclic hexadepsipeptides) [16]. Dalfopristin and quinopristin are representative example of the streptogramin A and streptogramin B groups, respectively.…”

Section: Streptogramin Antibioticsmentioning

confidence: 99%

Classification of Anti‐Bacterial Agents and Their Functions

Ullah¹,

Ali²

2017

Antibacterial Agents

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Bacteria that cause bacterial infections and disease are called pathogenic bacteria. They cause diseases and infections when they get into the body and begin to reproduce and crowd out healthy bacteria or to grow into tissues that are normally sterile. To cure infectious diseases, researchers discovered antibacterial agents, which are considered to be the most promising chemotherapeutic agents. Keeping in mind the resistance phenomenon developing against antibacterial agents, new drugs are frequently entering into the market along with the existing drugs. In this chapter, we discussed a revised classification and function of the antibacterial agent based on a literature survey. The antibacterial agents can be classified into five major groups, i.e. type of action, source, spectrum of activity, chemical structure, and function.

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“…Streptogramins are potent drugs against numerous highly resistant pathogens and therefore are used as antibiotics therapy of last-resort in humans. They consist of a mixture of two different types of chemical substances -the group A streptogramins, which are polyunsaturated macrolactones; and the group B streptogramins, representing cyclic hexadepsipeptides (Mast and Wohlleben, 2014;Patel and Gallagher, 2015). Vnicymainigri was obtained by fermentation of the culture of Streptomyces G-89 (Nomura et al, 1987), and it contained fatty acid [33].…”

Section: Branched Saturated and Unsaturated Fatty Acidsmentioning

confidence: 99%

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

Dembitsky¹

2017

Int. J. Curr. Res. Biosci. Plant Biol.

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A b s t r a c t A r t i c l e I n f oThis review is a comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes. Lots of fungal peptides display important biological activities of interest, which includes antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, immunosuppressive properties, and other pharmacological activities. There is no doubt that they are of great importance, especially in medicinal chemistry and/or pharmaceutical application. This review presents structures of more than 150 fatty acids, incorporated into marine and terrestrial fungal lipopeptides.

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Streptogramins – Two are better than one!

Cited by 94 publications

References 64 publications

PapR6, a Putative Atypical Response Regulator, Functions as a Pathway-Specific Activator of Pristinamycin II Biosynthesis in Streptomyces pristinaespiralis

PapR6, a Putative Atypical Response Regulator, Functions as a Pathway-Specific Activator of Pristinamycin II Biosynthesis in Streptomyces pristinaespiralis

Classification of Anti‐Bacterial Agents and Their Functions

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

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