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  1. AU="Munro, Lachlan Jake"
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  1. Article: Analysis of a Library of

    Munro, Lachlan Jake / Kell, Douglas B

    Antibiotics (Basel, Switzerland)

    2022  Volume 11, Issue 8

    Abstract: Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase ... ...

    Abstract Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting these transporters is a potential avenue to combat antibiotic resistance. In this study, we used an automated screening pipeline to evaluate the growth of a library of 447
    Language English
    Publishing date 2022-08-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics11081129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identification of transporters involved in aromatic compounds tolerance through screening of transporter deletion libraries.

    Sáez-Sáez, Javier / Munro, Lachlan Jake / Møller-Hansen, Iben / Kell, Douglas B / Borodina, Irina

    Microbial biotechnology

    2024  Volume 17, Issue 4, Page(s) e14460

    Abstract: Aromatic compounds are used in pharmaceutical, food, textile and other industries. Increased demand has sparked interest in exploring biotechnological approaches for their sustainable production as an alternative to chemical synthesis from petrochemicals ...

    Abstract Aromatic compounds are used in pharmaceutical, food, textile and other industries. Increased demand has sparked interest in exploring biotechnological approaches for their sustainable production as an alternative to chemical synthesis from petrochemicals or plant extraction. These aromatic products may be toxic to microorganisms, which complicates their production in cell factories. In this study, we analysed the toxicity of multiple aromatic compounds in common production hosts. Next, we screened a subset of toxic aromatics, namely 2-phenylethanol, 4-tyrosol, benzyl alcohol, berberine and vanillin, against transporter deletion libraries in Escherichia coli and Saccharomyces cerevisiae. We identified multiple transporter deletions that modulate the tolerance of the cells towards these compounds. Lastly, we engineered transporters responsible for 2-phenylethanol tolerance in yeast and showed improved 2-phenylethanol bioconversion from L-phenylalanine, with deletions of YIA6, PTR2 or MCH4 genes improving titre by 8-12% and specific yield by 38-57%. Our findings provide insights into transporters as targets for improving the production of aromatic compounds in microbial cell factories.
    MeSH term(s) Phenylethyl Alcohol ; Saccharomyces cerevisiae ; Benzyl Alcohol ; Biotechnology ; Escherichia coli ; Membrane Transport Proteins ; Organic Chemicals
    Chemical Substances Phenylethyl Alcohol (ML9LGA7468) ; Benzyl Alcohol (LKG8494WBH) ; Membrane Transport Proteins ; Organic Chemicals
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2406063-X
    ISSN 1751-7915 ; 1751-7915
    ISSN (online) 1751-7915
    ISSN 1751-7915
    DOI 10.1111/1751-7915.14460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT

    López-Sánchez, Uriel / Munro, Lachlan Jake / Ladefoged, Lucy Kate / Pedersen, Anders Juel / Brun, Christian Colding / Lyngby, Signe Meisner / Baud, Delphine / Juillan-Binard, Céline / Pedersen, Miriam Grønborg / Lummis, Sarah C R / Bang-Andersen, Benny / Schiøtt, Birgit / Chipot, Christophe / Schoehn, Guy / Neyton, Jacques / Dehez, Francois / Nury, Hugues / Kristensen, Anders S

    Nature structural & molecular biology

    2024  

    Abstract: Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5- ... ...

    Abstract Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT
    Language English
    Publishing date 2024-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-024-01282-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Automating Cloning by Natural Transformation.

    Jiang, Xinglin / Palazzotto, Emilia / Wybraniec, Ewa / Munro, Lachlan Jake / Zhang, Haibo / Kell, Douglas B / Weber, Tilmann / Lee, Sang Yup

    ACS synthetic biology

    2020  Volume 9, Issue 12, Page(s) 3228–3235

    Abstract: Affordable and automated cloning platforms are essential to many synthetic biology studies. However, the ... ...

    Abstract Affordable and automated cloning platforms are essential to many synthetic biology studies. However, the traditional
    MeSH term(s) Acinetobacter/genetics ; Acinetobacter/metabolism ; Automation ; Biological Products/metabolism ; Cloning, Molecular ; DNA/chemistry ; DNA/metabolism ; Escherichia coli/genetics ; Multigene Family/genetics ; Polymerase Chain Reaction ; Transformation, Genetic/physiology
    Chemical Substances Biological Products ; DNA (9007-49-2)
    Language English
    Publishing date 2020-11-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2161-5063
    ISSN (online) 2161-5063
    DOI 10.1021/acssynbio.0c00240
    Database MEDical Literature Analysis and Retrieval System OnLINE

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