Natural products from myxobacteria: novel metabolites and bioactivities

Herrmann, Jennifer; Fayad, Antoine Abou; Müller, Rolf

doi:10.1039/c6np00106h

Cited by 204 publications

(184 citation statements)

References 157 publications

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“…[3,4] Thev alue of natural products as direct source, precursor,o ri nspiration for novel antibacterial drugs is of special importance as the majority of approved compounds are derived from such structures. [6,7] Therecent discovery of the bacterial gyrase inhibitors cystobactamids (1) [8,9] and their derivatives,namely coralmycins [10] and the structurally similar albicidins, [11,12] impressively show that promising antibiotics that are active against Gram-negative bacteria can still be found. [6,7] Therecent discovery of the bacterial gyrase inhibitors cystobactamids (1) [8,9] and their derivatives,namely coralmycins [10] and the structurally similar albicidins, [11,12] impressively show that promising antibiotics that are active against Gram-negative bacteria can still be found.…”

Section: Microbialresistanceisincreasingworldwideandthepublicmentioning

confidence: 99%

Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram‐Negative Pathogens

et al. 2017

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Antibiotic discovery and development is challenging as chemical scaffolds of synthetic origin often lack the required pharmaceutical properties, and the discovery of novel ones from natural sources is tedious. Herein, we report the discovery of new cystobactamids with a significantly improved antibacterial profile in a detailed screening of myxobacterial producer strains. Some of these new derivatives display antibacterial activities in the low-μg mL range against Gram-negative pathogens, including clinical isolates of Klebsiella oxytoca, Pseudomonas aeruginosa, and fluoroquinolone-resistant Enterobacteriaceae, which were not observed for previously reported cystobactamids. Our findings provide structure-activity relationships and show how pathogen resistance can be overcome by natural scaffold diversity. The most promising derivative 861-2 was prepared by total synthesis, enabling further chemical optimization of this privileged scaffold.

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Section: Microbialresistanceisincreasingworldwideandthepublicmentioning

confidence: 99%

Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram‐Negative Pathogens

et al. 2017

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“…They have a very large genome size compared to other bacteria, and a number of structurally unique biologically active secondary metabolites are produced by this group of bacteria (Wenzel and Muller 2009;Han et al 2013;Reichenbach 2001). Many compounds isolated from myxobacteria act on unique cellular targets, which, at the time of their discovery, were not targeted by other secondary metabolites (Bode and Muller 2006;Herrmann et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Molecular and functional characterization of myxobacteria isolated from soil in India

et al. 2017

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This study reports the isolation of myxobacteria from soil collected from plains in north India. Based on the morphology and 16S rDNA sequence, the isolated myxobacteria were identified as Corallococcus sp., Pyxidicoccus sp., Myxococcus sp., Cystobacter sp. and Archangium sp. The myxobacteria were functionally characterized to assess their ability to produce antibacterial and anticancer metabolites. The isolates were found to be functionally versatile as they produced extracellular bioactive molecules that exhibited high frequency of activities against Bacillus cereus, Mycobacterium smegmatis, Enterobacter cloacae and Pseudomonas syringae. The strains also showed cytotoxic activity against the human cancer cell lines of liver, pancreas, prostrate, bone and cervix. These results indicate the importance of isolating diverse strains of myxobacteria from unexplored habitats to find novel bioactive compounds. Moreover, the bioactive molecules explored in this study are predominantly hydrophilic compounds, obviating the limitations of solubility-related aspect of drug discovery.

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“…The genome of D. discoideum for example harbors around4 0 polyketide synthase genes, and D. purpureum displays as imilar number. [6] Althought hese amoebae have not been studied as extensively as actinobacteria, [7] myxobacteria, [8] pseudomonads, [9] or variousf ungi, [10] ad iverse set of natural products have been isolated from them. Typically,t hese amoebal secondary metabolites have miniscule production rates when the organisms are cultured under standard laboratory conditions, hindering their isolation,s tructure elucidation, and subsequent biological testing.…”

Section: Introductionmentioning

confidence: 99%

Natural Products from Social Amoebae

Barnett

Stallforth

2017

Chemistry A European J

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Natural products are invaluable sources of structural diversity and complexity ideally suited for the development of therapeutic agents. The search for novel bioactive molecules has prompted scientists to explore various ecological niches. Microorganisms have been shown to constitute such an important source. Despite their biosynthetic potential, social amoebae, that is, microorganisms with both a uni- and multicellular lifestyle, are underexplored regarding their secreted secondary metabolome. In this review, we present the structural diversity of amoebal natural products and discuss their biological functions as well as their total syntheses.

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Natural products from myxobacteria: novel metabolites and bioactivities

Cited by 204 publications

References 157 publications

Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram‐Negative Pathogens

Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram‐Negative Pathogens

Molecular and functional characterization of myxobacteria isolated from soil in India

Natural Products from Social Amoebae

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