scholarly journals Novel Fredericamycin Variant Overproduced by a Streptomycin-Resistant Streptomyces albus subsp. chlorinus Strain

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 284
Author(s):  
Marta Rodríguez Estévez ◽  
Maksym Myronovskyi ◽  
Birgit Rosenkränzer ◽  
Thomas Paululat ◽  
Lutz Petzke ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
The Novel ◽  
Antibiotic Resistant ◽  
Fredericamycin A ◽  
Drug Lead ◽  
Streptomyces Albus ◽  
Polyketide Synthase Gene ◽  
Resistant Mutants ◽  
Marine Strain ◽  
Natural Drugs

Streptomycetes are an important source of natural products potentially applicable in the pharmaceutical industry. Many of these drugs are secondary metabolites whose biosynthetic genes are very often poorly expressed under laboratory cultivation conditions. In many cases, antibiotic-resistant mutants exhibit increased production of natural drugs, which facilitates the identification and isolation of new substances. In this study, we report the induction of a type II polyketide synthase gene cluster in the marine strain Streptomyces albus subsp. chlorinus through the selection of streptomycin-resistant mutants, resulting in overproduction of the novel compound fredericamycin C2 (1). Fredericamycin C2 (1) is structurally related to the potent antitumor drug lead fredericamycin A.

scholarly journals Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 435 ◽  
Author(s):  
Marta Rodríguez Estévez ◽  
Maksym Myronovskyi ◽  
Nils Gummerlich ◽  
Suvd Nadmid ◽  
Andriy Luzhetskyy
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Gene Clusters ◽  
Growth Conditions ◽  
Pharmaceutical Drugs ◽  
Gyra Gene ◽  
Streptomyces Albus ◽  
Potential Applications ◽  
Resistant Mutants ◽  
Marine Strain

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial pharmaceutical drugs. Here, we report the identification of the previously uncharacterized nybomycin gene cluster from the marine actinomycete Streptomyces albus subsp. chlorinus through its heterologous expression. Nybomycin has previously been reported to act against quinolone-resistant Staphylococcus aureus strains harboring a mutated gyrA gene but not against those with intact gyrA. The nybomycin-resistant mutants generated from quinolone-resistant mutants have been reported to be caused by a back-mutation in the gyrA gene that restores susceptibility to quinolones. On the basis of gene function assignment from bioinformatics analysis, we suggest a model for nybomycin biosynthesis.

Molecular Docking Approaches to Suggest the Anti-Mycobacterial Targets of Natural Products

2020 ◽  
Author(s):  
Rafael Baptista ◽  
Sumana Bhowmick ◽  
Shen Jianying ◽  
Luis Mur
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Free Energies ◽  
Antibiotic Resistant ◽  
Drug Lead ◽  
Bisbenzylisoquinoline Alkaloids ◽  
Docking Approach ◽  
Global Threat ◽  
Physicochemical And Structural Properties

Tuberculosis (TB) is a major global threat mostly due to the development of antibiotic resistant forms of Mycobacterium tuberculosis, the causal agent of the disease. Driven by the pressing need for new anti-mycobacterial agents, several natural products (NPs) have been shown to have in vitro activities against M. tuberculosis. The utility of any NP as a drug lead is augmented when the anti-mycobacterial target(s) is unknown. To suggest these, we used a molecular docking approach to predict the interactions of 53 selected anti-mycobacterial NPs against known ‘druggable’ mycobacterial targets ClpP1P2, DprE1, InhA, KasA, PanK, PknB and Pks13. The docking scores / binding free energies were predicted and calculated using AutoDock Vina along with physicochemical and structural properties of the NPs, using PaDEL descriptors. These were compared to the established inhibitor (control) drugs for each mycobacterial target. The specific interactions of the bisbenzylisoquinoline alkaloids 2-nortiliacorinine, tiliacorine and 13’-bromotiliacorinine against the targets PknB and DprE1 (-11.4, -10.9 and -9.8 kcal.mol-1 ; -12.7, -10.9 and -10.3 kcal.mol-1 , respectively) and the lignan αcubebin and Pks13 (-11.0 kcal.mol-1 ) had significantly superior docking scores compared to controls. Our approach can be used to suggest predicted targets for the NP to be validated experimentally but these in silico steps are likely to facilitate drug optimisation.

pks63787, a Polyketide Synthase Gene Responsible for the Biosynthesis of Benzenoids in the Medicinal Mushroom Antrodia cinnamomea

2016 ◽  
Vol 79 (6) ◽  
pp. 1485-1491 ◽  
Author(s):  
Po-Wei Yu ◽  
Ya-Chih Chang ◽  
Ruey-Fen Liou ◽  
Tzong-Huei Lee ◽  
Shean-Shong Tzean
Keyword(s):  
Polyketide Synthase ◽  
Medicinal Mushroom ◽  
Antrodia Cinnamomea ◽  
Polyketide Synthase Gene

scholarly journals Susceptibility of Virulent Yersinia pestis Bacteria to Predator Bacteria in the Lungs of Mice

2018 ◽  
Vol 7 (1) ◽  
pp. 2 ◽  
Author(s):  
Riccardo Russo ◽  
Irina Kolesnikova ◽  
Thomas Kim ◽  
Shilpi Gupta ◽  
Androulla Pericleous ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Bacterial Infections ◽  
Treatment Modalities ◽  
The Novel ◽  
Global Public Health ◽  
Antibiotic Resistant ◽  
Colony Forming Units ◽  
Tier 1 ◽  
Predatory Bacteria ◽  
Lethal Doses

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future.

scholarly journals Identification of a putative polyketide synthase gene involved in usnic acid biosynthesis in the lichen Nephromopsis pallescens

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0199110 ◽  
Author(s):  
Yi Wang ◽  
Changan Geng ◽  
Xiaolong Yuan ◽  
Mei Hua ◽  
Fenghua Tian ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Usnic Acid ◽  
Acid Biosynthesis ◽  
Polyketide Synthase Gene

Identification of a polyketide synthase gene ( pksP ) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence

1998 ◽  
Vol 187 (2) ◽  
pp. 79-89 ◽  
Author(s):  
K. Langfelder ◽  
Bernhard Jahn ◽  
Heike Gehringer ◽  
Axel Schmidt ◽  
Gerhard Wanner ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Polyketide Synthase ◽  
Polyketide Synthase Gene ◽  
Pigment Biosynthesis

Using spontaneous antibiotic-resistant mutants to assess competitiveness of bradyrhizobial inoculants for nodulation of soybean

1998 ◽  
Vol 44 (8) ◽  
pp. 753-758 ◽  
Author(s):  
Martha E Ramirez ◽  
Daniel W Israel ◽  
Arthur G Wollum II
Keyword(s):  
Parental Strain ◽  
Field Experiments ◽  
Antibiotic Resistant ◽  
Rooting Zone ◽  
Soil Systems ◽  
Yeast Extract Mannitol ◽  
Soil Media ◽  
Resistant Mutants ◽  
Cape Fear ◽  
Antibiotic Resistant Mutants

Spontaneous mutants (3/parental strain) of soybean bradyrhizobia resistant to streptomycin and erythromycin were selected from strains isolated from bradyrhizobial populations indigenous to Cape Fear and Dothan soils. These were used to evaluate (i) the validity of using antibiotic-resistant mutants to make inferences about the competitiveness of parental strains in soil environments and (ii) the recovery of strains in nodules after inoculation of soybeans grown in soils with indigenous bradyrhizobial populations. Streptomycin and erythromycin resistances of all mutants were stable after approximately 27 generations of growth in yeast extract - mannitol medium, but 33% of the mutants lost resistance to erythromycin upon passage through nodules. Only 17% of the mutants were as competitive as their parental strain when inoculated in a ratio near 1:1 in vermiculite. Four of 10 mutants, which differed in competitiveness from their parental strain in vermiculite, had competitiveness against the soil populations equal to that of their parental strain. Therefore, assessment of competitiveness of mutants and parental strains in non-soil media may not accurately reflect their competitiveness in soil systems. For both the Cape Fear and Dothan soils, recovery of a given mutant from nodules of field-grown plants was always lower than from nodules of plants grown in the greenhouse. Inoculation of the entire rooting zone in the greenhouse experiment and of only a portion of the rooting zone in the field experiments may account for this difference in recovery. Techniques that increase the volume of soil inoculated may enhance nodulation by inoculant strains.Key words: Bradyrizobium, antibiotic resistance, competition.

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