A Novel Enzyme Conferring Streptothricin Resistance Alters the Toxicity of Streptothricin D from Broad-spectrum to Bacteria-specific

Hamano, Yoshimitsu; Matsuura, Nobuo; Kitamura, M; Takagi, Hiroshi

doi:10.1074/jbc.m602294200

Cited by 28 publications

(39 citation statements)

References 32 publications

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“…Although many streptothricinresistance genes have been identified, only one resistance mechanism has been identified. A novel streptothricinresistance gene (SttH) was successfully isolated from S. albulus [14]. An SttH gene-knockout mutant to better understand the true biologicol role of SttH in S. albulus and to clarify whether or not S. albulus possesses different streptothricin-resistance gene(s) was also constructed [15].…”

Section: Introductionmentioning

confidence: 99%

Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov

Wang

Zhang

et al. 2007

J Antibiot

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Four streptothricin-group antibiotics (1ϳ4) were isolated from the fermentation broth of Streptomyces qinlingensis sp. nov. Along with the known antibiotics streptothricins F (1) and D (3), two new members of this class (2, 4) were identified as 12-carbamoyl derivatives of 1 and 3, respectively, mainly by analysis of the IR, HR-MS and NMR spectral data. The antibacterial activities of 1ϳ4 against Escherichia coli (MICs 3.1, 25.0, 3.1 and 12.5 m g/ml), Bacillus subtilis (MICs 6.3, 25.0, 3.1 and 50 m g/ml), Staphylococcus aureus (MICs 12.5, Ͼ100.0, 6.3, Ͼ100.0 mg/ml), Bacillus cereus (MICs 25.0, 50.0, 25.0 and 50.0 mg/ml) and Pseudomonas aeruginosa (MICs 50.0, Ͼ100.0, 50.0, Ͼ100.0mg/ml) were assayed by micro-broth dilution. The results based on MIC data indicated that 2 and 4 exhibited significantly less potent antibacterial activities when compared to that of 1 and 3.

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Section: Introductionmentioning

confidence: 99%

Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov

Wang

Zhang

et al. 2007

J Antibiot

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“…7,8 The results may be attributed to that, although STs possess easily hydrolyzable bonds, such as ester and amido bonds, but the hydrolysis is strongly influenced by the number of b-lysine. In 2006, Hamano et al 6 isolated a novel ST-resistance gene (sttH) from S. albulus, which could catalyze the transformation of ST-D and ST-F from lactam to acid in vitro. The results of HPLC-MS/MS analysis also indicated the distribution of ST acids in the metabolites of S. qinlingensis.…”

Section: Structure Elucidationmentioning

confidence: 99%

“…7,8 In addition, only the bio-activities of ST-F and ST-D acids have been investigated. 6 In the process of screening for new antibiotics, S. qinlingensis, a ST producer, was isolated from soil samples. ST-F, ST-D and two other novel compounds, 12-carbamoyl-ST-F and 12-carbamoyl-ST-D, have been isolated from its fermentation broth in our laboratory.…”

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confidence: 99%

“…Although they were shown to possess strong antimicrobial activity against many species of fungi and bacteria, their application in the therapeutic area has been hampered because of the nephrotoxicity. [2][3][4][5] Hamano et al 6 isolated a novel ST-resistance gene (sttH) and showed that the hydrolysis of the amide bond of streptolidine lactam could be catalyzed by the enzyme in vitro. With the breaking of the amide bond, the antimicrobial activity of streptothricin D (ST-D) was altered from broad-spectrum to bacteria-specific, and its toxicity against eukaryotic cells was also reduced at the same time.…”

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confidence: 99%

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Isolation, structure elucidation and antibacterial activities of streptothricin acids

Ji¹,

Wang

Sang³

et al. 2009

J Antibiot

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Five streptothricin acids (compounds 1-5) were isolated by ion-exchange resin chromatography and preparative RP-HPLC from the fermentation broth of Streptomyces qinlingensis. Their structures were elucidated mainly by analyses of the IR, HR-EIS-MS and NMR spectral data. They were deduced as two known compounds, streptothricin F acid (1) and streptothricin D acid (2), and three new compounds, 12-carbamoylstreptothricin E acid (3), 12-carbamoylstreptothricin D acid (4) and N-acetylstreptothricin D acid (5) Keywords: antibacterial activity; streptothricin acid; structural elucidation Streptothricin antibiotic is a type of broad-spectrum antibiotics. As streptothricin F was isolated from Streptomyces lavendulae in 1942, 1 dozens of streptothricins (STs) have been isolated from natural resources. Although they were shown to possess strong antimicrobial activity against many species of fungi and bacteria, their application in the therapeutic area has been hampered because of the nephrotoxicity. [2][3][4][5] Hamano et al. 6 isolated a novel ST-resistance gene (sttH) and showed that the hydrolysis of the amide bond of streptolidine lactam could be catalyzed by the enzyme in vitro. With the breaking of the amide bond, the antimicrobial activity of streptothricin D (ST-D) was altered from broad-spectrum to bacteria-specific, and its toxicity against eukaryotic cells was also reduced at the same time. These results suggest that ST-D acid is a potential candidate for clinical development or use as a new lead compound for drug discovery. Attempts at preparing ST acids were made from STs chemically, but only ST-F acid, which bears one b-lysine, was readily obtained, whereas others that bear more b-lysine residues were not prepared successfully. 7,8 In addition, only the bio-activities of ST-F and ST-D acids have been investigated. 6 In the process of screening for new antibiotics, S. qinlingensis, a ST producer, was isolated from soil samples. ST-F, ST-D and two other novel compounds, 12-carbamoyl-ST-F and 12-carbamoyl-ST-D, have been isolated from its fermentation broth in our laboratory. 9 In subsequent research, a facile LC-MS/MS method based on RP-HPLC coupled with electrospray ionization tandem mass spectrometry was used for the analysis of STs in the fermentation broth of S. qinlingensis. 10 A total of 19 ST-like compounds were identified or tentatively characterized on the basis of their mass spectral data; among them, 12 were ST acids. Here, we report the isolation, structure elucidation and antibacterial activities of five ST acids that were isolated by ion-exchange resin chromatography and preparative RP-HPLC from the fermentation broth of S. qinlingensis. These compounds were identified as two known compounds, ST-F acid (1) and ST-D acid (2), and three new compounds, 12-carbamoylstreptothricin E acid (3), 12-carbamoylstreptothricin D acid (4) and N-acetylstreptothricin D acid (5). The antibacterial activities of 1-5 against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Bacillus cereus and Pseudomonas ...

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“…ST-F, ST-D and ST-C were purified from the ST-mix by reverse-phase HPLC. 16 Other chemicals were of reagent grade, and were used as received.…”

Section: Chemicalsmentioning

confidence: 99%

Promotion Effect of Streptothricin on a Glucose Oxidase Enzymatic Reaction and Its Application to a Colorimetric Assay

et al. 2018

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A Novel Enzyme Conferring Streptothricin Resistance Alters the Toxicity of Streptothricin D from Broad-spectrum to Bacteria-specific

Cited by 28 publications

References 32 publications

Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov

Two New Members of Streptothricin Class Antibiotics from Streptomyces qinlingensis sp. nov

Isolation, structure elucidation and antibacterial activities of streptothricin acids

Promotion Effect of Streptothricin on a Glucose Oxidase Enzymatic Reaction and Its Application to a Colorimetric Assay

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