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  • Frontiers Media SA  (2)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Sustainable Food Systems Vol. 5 ( 2021-3-23)
    In: Frontiers in Sustainable Food Systems, Frontiers Media SA, Vol. 5 ( 2021-3-23)
    Abstract: The One Strain Many Compounds approach (OSMAC) is a powerful and comprehensive method that enables the chemo-diversity evaluation of microorganisms. This is achieved by variations of physicochemical cultivation parameters and by providing biotic and abiotic triggers to mimic microorganisms' natural environment in the lab. This approach can reactivate the silent biosynthetic routes of specific metabolites typically not biosynthesized under standard laboratory conditions. In the present study, we combined the OSMAC approach with static headspace solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS), high-performance liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMS n ), and matrix-assisted laser desorption/ionization high-resolution mass spectrometry imaging (MALDI-HRMSI) to evaluate the chemoecological significance of an apple root-associated endophytic Streptomyces pulveraceus strain ES16. We employed the OSMAC approach by cultivating the endophyte in six different media conditions and performed temporal studies over 14 days. Analysis of the volatilome revealed that only under stressful conditions associated with sporulation, endophytic S. pulveraceus ES16 produces geosmin, a volatile semiochemical known to attract the soil arthropods Collembola (springtails) specifically. Subsequently, targeted metabolic profiling revealed polycyclic tetramate macrolactams (PTMs) production by the endophyte under stress, which are bioactive against various pathogens. Additionally, the endophyte produced the iron-chelating siderophore, mirubactin, under the same conditions. The structures of the compounds were evaluated using HRMS n and by comparison with literature data. Finally, MALDI-HRMSI revealed the produced compounds' spatial-temporal distribution over 14 days. The compounds were profusely secreted into the medium after production. Our results indicate that endophytic S. pulveraceus ES16 can release the signal molecule geosmin, chemical defense compounds such as the PTMs, as well as the siderophore mirubactin into the host plant apoplast or the soil for ecologically meaningful purposes, which are discussed.
    Type of Medium: Online Resource
    ISSN: 2571-581X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2928540-9
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Bioengineering and Biotechnology Vol. 11 ( 2023-2-2)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 11 ( 2023-2-2)
    Abstract: In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical (CL) homogeneous compartment pharmacodynamic (PD) models and a spatial-temporal (ST), multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmacokinetic curve (AUC) of the drug blood concentration. We find that an CL-model based on a well-mixed blood compartment is sufficient to correctly predict the in vivo toxicity from in vitro data. However, the ST-model that integrates more experimental information requires a change of at least one parameter to obtain the same prediction, indicating that spatial compartmentalization may indeed be an important factor.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2719493-0
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