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  1. Article: Aurachins, Bacterial Antibiotics Interfering with Electron Transport Processes.

    Kruth, Sebastian / Nett, Markus

    Antibiotics (Basel, Switzerland)

    2023  Volume 12, Issue 6

    Abstract: Aurachins are farnesylated quinolone alkaloids of bacterial origin and excellent inhibitors of the respiratory chain in pro- and eukaryotes. Therefore, they have become important tool compounds for the investigation of electron transport processes and ... ...

    Abstract Aurachins are farnesylated quinolone alkaloids of bacterial origin and excellent inhibitors of the respiratory chain in pro- and eukaryotes. Therefore, they have become important tool compounds for the investigation of electron transport processes and they also serve as lead structures for the development of antibacterial and antiprotozoal drugs. Especially aurachin D proved to be a valuable starting point for structure-activity relationship studies. Aurachin D is a selective inhibitor of the cytochrome
    Language English
    Publishing date 2023-06-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics12061067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Biocatalytic production of the antibiotic aurachin D in Escherichia coli.

    Kruth, Sebastian / Schibajew, Lina / Nett, Markus

    AMB Express

    2022  Volume 12, Issue 1, Page(s) 138

    Abstract: Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with ... ...

    Abstract Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with recombinant Escherichia coli cells expressing the biosynthesis enzyme AuaA. In order to achieve a high-level production of this membrane-bound farnesyltransferase in E. coli, the expression of the auaA gene was translationally coupled to an upstream cistron in accordance with a bicistronic design (BCD) strategy. Screening of various BCD elements led to the identification of optimized auaA expression cassettes, which increased the aurachin D titer in E. coli up to 29-fold in comparison to T7-mediated expression. This titer could be further raised by codon optimization of auaA and by introducing the mevalonate pathway into the production strain. The latter measure was intended to improve the availability of farnesyl pyrophosphate, which is needed as a cosubstrate for the AuaA-catalyzed reaction. In sum, the described efforts resulted in a strain producing aurachin D with a titer that is 424 times higher than that obtained with the original, non-optimized expression host.
    Language English
    Publishing date 2022-11-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2621432-5
    ISSN 2191-0855
    ISSN 2191-0855
    DOI 10.1186/s13568-022-01478-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Generation of Aurachin Derivatives by Whole-Cell Biotransformation and Evaluation of Their Antiprotozoal Properties.

    Kruth, Sebastian / Zimmermann, Cindy J-M / Kuhr, Katharina / Hiller, Wolf / Lütz, Stephan / Pietruszka, Jörg / Kaiser, Marcel / Nett, Markus

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 3

    Abstract: The natural product aurachin D is a farnesylated quinolone alkaloid, which is known to possess activity against the causative agent of malaria, ...

    Abstract The natural product aurachin D is a farnesylated quinolone alkaloid, which is known to possess activity against the causative agent of malaria,
    MeSH term(s) Humans ; Trypanosoma cruzi ; Escherichia coli ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/chemistry ; Chagas Disease ; Leishmania donovani ; Biotransformation ; Quinolones/pharmacology ; Biological Products/pharmacology ; Plasmodium falciparum ; Parasitic Sensitivity Tests
    Chemical Substances Antiprotozoal Agents ; Quinolones ; Biological Products
    Language English
    Publishing date 2023-01-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28031066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  4. Article: Mutasynthesis of Physostigmines in Myxococcus xanthus

    Winand, Lea / Schneider, Pascal / Kruth, Sebastian / Greven, Nico-Joel / Hiller, Wolf / Kaiser, Marcel / Pietruszka, Jörg / Nett, Markus

    Organic letters. 2021 Aug. 06, v. 23, no. 16

    2021  

    Abstract: The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of ... ...

    Abstract The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.
    Keywords Myxococcus xanthus ; genetically modified organisms ; physostigmine ; synthesis ; therapeutics ; toxicity
    Language English
    Dates of publication 2021-0806
    Size p. 6563-6567.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1523-7052
    DOI 10.1021/acs.orglett.1c02374
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Mutasynthesis of Physostigmines in

    Winand, Lea / Schneider, Pascal / Kruth, Sebastian / Greven, Nico-Joel / Hiller, Wolf / Kaiser, Marcel / Pietruszka, Jörg / Nett, Markus

    Organic letters

    2021  Volume 23, Issue 16, Page(s) 6563–6567

    Abstract: The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of ... ...

    Abstract The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host
    MeSH term(s) Molecular Structure ; Myxococcus xanthus/chemistry ; Myxococcus xanthus/metabolism ; Physostigmine/analogs & derivatives ; Physostigmine/chemistry ; Physostigmine/metabolism
    Chemical Substances Physostigmine (9U1VM840SP) ; phenserine (SUE285UG3S)
    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1523-7052
    ISSN (online) 1523-7052
    DOI 10.1021/acs.orglett.1c02374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Shifts in Campylobacter species abundance may reflect general microbial community shifts in periodontitis progression.

    Henne, Karsten / Fuchs, Felix / Kruth, Sebastian / Horz, Hans-Peter / Conrads, Georg

    Journal of oral microbiology

    2014  Volume 6, Page(s) 25874

    Abstract: Background: Oral Campylobacter species have been found to be associated with periodontitis progression. While the etiological significance of Campylobacter rectus is quite established, the association of C. gracilis, C. concisus, and C. curvus with ... ...

    Abstract Background: Oral Campylobacter species have been found to be associated with periodontitis progression. While the etiological significance of Campylobacter rectus is quite established, the association of C. gracilis, C. concisus, and C. curvus with health or disease remains contradictory.
    Objectives: This study hypothesizes that the proportion of species within the Campylobacter genus rather than the absolute abundance of a single species is a suitable indicator for periodontitis progression.
    Design: Subgingival plaque from 90 periodontitis patients and gingival sulcus fluid of 32 healthy individuals were subjected to a newly developed nested PCR approach, in which all Campylobacter spp. were amplified simultaneously. The resulting mixture of 16S-rRNA-gene-amplicons were separated by single-stranded conformation polymorphism (SSCP) gel electrophoresis, followed by sequencing and identification of excised bands and relative quantification of band intensities. In all samples, the abundance of selected periodontitis marker species was determined based on DNA hybridization on a microarray.
    Results: The highly prevalent Campylobacter community was composed of varying proportions of C. rectus, C. gracilis, C. concisus, and C. curvus. Cluster analysis based on SSCP-banding pattern resulted in distinct groups which in turn coincided with significant differences in abundance of established periodontitis marker species (Tannerella forsythia, Porphyromonas gingivalis, and Fusobacterium nucleatum) and progression.
    Conclusions: The shift in the Campylobacter community composition seems to display the general microbial community shift during clinical progression in a simplified manner. The focus on members of the Campylobacter in this study suggests that this genus can be an indicator of ecological changes in the subgingival oral microflora.
    Language English
    Publishing date 2014-11-19
    Publishing country United States
    Document type Journal Article
    ISSN 2000-2297
    ISSN 2000-2297
    DOI 10.3402/jom.v6.25874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Integration of Genetic and Process Engineering for Optimized Rhamnolipid Production Using

    Tiso, Till / Ihling, Nina / Kubicki, Sonja / Biselli, Andreas / Schonhoff, Andreas / Bator, Isabel / Thies, Stephan / Karmainski, Tobias / Kruth, Sebastian / Willenbrink, Anna-Lena / Loeschcke, Anita / Zapp, Petra / Jupke, Andreas / Jaeger, Karl-Erich / Büchs, Jochen / Blank, Lars M

    Frontiers in bioengineering and biotechnology

    2020  Volume 8, Page(s) 976

    Abstract: Rhamnolipids are biosurfactants produced by microorganisms with the potential to replace synthetic compounds with petrochemical origin. To promote industrial use of rhamnolipids, recombinant rhamnolipid production from sugars needs to be intensified. ... ...

    Abstract Rhamnolipids are biosurfactants produced by microorganisms with the potential to replace synthetic compounds with petrochemical origin. To promote industrial use of rhamnolipids, recombinant rhamnolipid production from sugars needs to be intensified. Since this remains challenging, the aim of the presented research is to utilize a multidisciplinary approach to take a step toward developing a sustainable rhamnolipid production process. Here, we developed expression cassettes for stable integration of the rhamnolipid biosynthesis genes into the genome outperformed plasmid-based expression systems. Furthermore, the genetic stability of the production strain was improved by using an inducible promoter. To enhance rhamnolipid synthesis, energy- and/or carbon-consuming traits were removed: mutants negative for the synthesis of the flagellar machinery or the storage polymer PHA showed increased production by 50%. Variation of time of induction resulted in an 18% increase in titers. A scale-up from shake flasks was carried out using a 1-L bioreactor. By recycling of the foam, biomass loss could be minimized and a rhamnolipid titer of up to 1.5 g/L was achieved without using mechanical foam destroyers or antifoaming agents. Subsequent liquid-liquid extraction was optimized by using a suitable minimal medium during fermentation to reduce undesired interphase formation. A technical-scale production process was designed and evaluated by a life-cycle assessment (LCA). Different process chains and their specific environmental impact were examined. It was found that next to biomass supply, the fermentation had the biggest environmental impact. The present work underlines the need for multidisciplinary approaches to address the challenges associated with achieving sustainable production of microbial secondary metabolites. The results are discussed in the context of the challenges of microbial biosurfactant production using hydrophilic substrates on an industrial scale.
    Language English
    Publishing date 2020-08-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2020.00976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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