Antibiotic drug discovery

Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

doi:10.1111/1751-7915.12388

Cited by 123 publications

(109 citation statements)

References 57 publications

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“…In particular, in the realm of Bacillales hundreds of genomes have been completely sequenced. This immense array of data has enabled the development of genome mining strategies for the detection, structure analysis, and exploitation of yet‐unknown bioactive compounds . Particularly successful procedures that combine bioinformatic genome screening with modern mass spectrometry by utilizing the unsurpassed sensitivity and accuracy of such techniques for the detection of novel compounds and for structure elucidation have been revealed …”

Section: Introductionmentioning

confidence: 99%

“…This immense array of data has enabledt he development of genome minings trategies for the detection, structure analysis, and exploitation of yet-unknown bioactive compounds. [1][2][3][4][5][6][7][8][9][10][11] Particularly successful procedures that combine bioinformatic genome screening with modernm ass spectrometry by utilizing the unsurpassed sensitivitya nd accuracyo f such techniques for the detection of novel compounds and for structure elucidation have been revealed. [5] Paenibacilli are ar ich source of attractive secondary metabolites, and among them, nonribosomal peptides (NRPs), polyketides (PKs), NRP-PK hybrids, and bacteriocins are of great interest for both agro-biotechnological and medicalu ses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genome Mining of the Lipopeptide Biosynthesis of Paenibacillus polymyxa E681 in Combination with Mass Spectrometry: Discovery of the Lipoheptapeptide Paenilipoheptin

et al. 2018

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Paenibacillus polymyxa strains are qualified for agro-biotechnological uses such as plant growth promotion and for biocontrol strategies against deleterious phytopathogenic competitors in the soil depending on their attractive arsenal of bioactive compounds. Moreover, they are potent producers of antibiotics for medical applications. To identify new products of such organisms, genome mining strategies in combination with mass spectrometry are the methods of choice. Herein, we performed such studies with the Paenibacillus strain E681. Bioinformatic evaluation of its genome sequence revealed four gene clusters A-D encoding nonribosomal peptide synthetases (NRPSs). Accordingly, four lipopeptide families were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Clusters A and D codify the well known fusaricidins and polymyxins. A yet-unknown lipoheptapeptide was discovered and structurally characterized by de novo sequencing by using MALDI-LIFT-TOF/TOF MS. It was designated as paenilipoheptin. From structure predictions we infer that the production of this agent is encoded by gene cluster C. Gene cluster B encodes the synthesis of tridecaptins, a family of open-chain lipotridecapeptides. Strain E681 produces new subspecies of such compounds (tridecaptins E) showing variations both in their fatty-acid part as well as in their peptide part.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome Mining of the Lipopeptide Biosynthesis of Paenibacillus polymyxa E681 in Combination with Mass Spectrometry: Discovery of the Lipoheptapeptide Paenilipoheptin

et al. 2018

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“…Each PKS module encodes various domains encoding several enzymes involved in programmed synthesis of newly polyketide compound. Nonribosomal Peptides (NRP) are a class of peptide secondary metabolites synthesized by nonribosomal peptide synthetases, which, unlike Metabolomics: Open Access the ribosomes, are independent of messenger RNA [7]. Often have cyclic and/or branched structures, can contain nonproteinogenic amino acids including D-amino acids, carry modifications like N-methyl and N-formyl groups, or are glycosylated, acylated, halogenated, or hydroxylated.…”

Section: Genome Base Screening Of Bioactive Actinomycetesmentioning

confidence: 99%

Bioactive Metabolites of Actinomycetes–Screening from Genomic and Metabolomic Approach

Banerjee¹

2017

Metabolomics

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The urgency for new and novel therapeutic agent has increased since last few decades by the serious advent of resistant pathogens and our lifestyle. The situation is becoming scary due to very less arrival of new antibiotics or other bioactive agents. Since past few years the concept of drug discovery has changed dramatically. Several modern strategies have adopted and by using different revolutionary tools and techniques and software based program it has now become easier to screen the potential strain as well as purify those highly demanding molecules. Few significant approaches that are being taken recent days to face the challenge, have discussed in this editorial.

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“…Hundreds of these natural products have been identified and developed as therapeutic agents against many infectious diseases (Berdy, 2005). Microbial natural metabolites still appear as the most promising sources of antibiotic in the future (Fernando, 2006;Wohlleben et al, 2016). Some of the important antibiotic producing microorganisms are of Streptomyces, Bacillus, Cephalosporium, and Penicillium that have been studied continuously for their ability to produce antibiotics (Brock and Madigan, 1991).…”

Section: Introductionmentioning

confidence: 99%

Isolation and screening of antibiotic producing actinomycetes from rhizosphere and agricultural soils

Muleta¹,

Assefa²

2018

Afr. J. Biotechnol.

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Antibiotics are secondary metabolites produced by microorganisms. Actinomycetes are the top producers of antibiotics. The study was designed to isolate and screen antibiotic producing actinomycetes obtained from rhizosphere of plants and agricultural soils. A total of 30 actinomycetes were isolated. Out of the 30 actinomycetes, 18 (60%) showed antimicrobial activities against one of the tested microorganisms of which 9 isolates were selected for their wide spectrum of antibiotic activities. In this study, isolates AAUBA5 and AAUBA30 were found to inhibit all of the test organisms, except Escherichia coli ATCC 25922. The latter was found to be the most resistant and was only inhibited by 3/18 (17%) of the isolates. The isolates were identified and characterized by cultural, morphological, physiological, and biochemical characteristics and found to be classified under the genus Streptomycetes. In order to extract the active compounds from isolates, fermentation was carried out on 9 isolates and the former was extracted by using ethyl acetate. Finally, isolate AAUBA13 was selected for further study based on spectrum activity from disc diffusion assay. Antimicrobial compound obtained from AAUBA13 isolate was separated and purified with thin layer chromatography (TLC), column chromatography, and preparative chromatography. The finding of this study, in general, showed that, antimicrobial compounds obtained from AAUBA13 demonstrate broad spectrum antimicrobial activity against Staphylococcus aureus ATCC25923, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC25853, S. aureus (clinical isolate), Shigella boydii (clinical isolate), Streptococcus pneumonia ATCC49619, and Candida albicans ATCC62376.

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Antibiotic drug discovery

Cited by 123 publications

References 57 publications

Genome Mining of the Lipopeptide Biosynthesis of Paenibacillus polymyxa E681 in Combination with Mass Spectrometry: Discovery of the Lipoheptapeptide Paenilipoheptin

Genome Mining of the Lipopeptide Biosynthesis of Paenibacillus polymyxa E681 in Combination with Mass Spectrometry: Discovery of the Lipoheptapeptide Paenilipoheptin

Bioactive Metabolites of Actinomycetes–Screening from Genomic and Metabolomic Approach

Isolation and screening of antibiotic producing actinomycetes from rhizosphere and agricultural soils

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