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Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach

Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO(3) or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal ex...

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Autores principales: Gao, Ying, Stuhldreier, Fabian, Schmitt, Laura, Wesselborg, Sebastian, Guo, Zhiyong, Zou, Kun, Mándi, Attila, Kurtán, Tibor, Liu, Zhen, Proksch, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672018/
https://www.ncbi.nlm.nih.gov/pubmed/33250887
http://dx.doi.org/10.3389/fmicb.2020.600983
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author Gao, Ying
Stuhldreier, Fabian
Schmitt, Laura
Wesselborg, Sebastian
Guo, Zhiyong
Zou, Kun
Mándi, Attila
Kurtán, Tibor
Liu, Zhen
Proksch, Peter
author_facet Gao, Ying
Stuhldreier, Fabian
Schmitt, Laura
Wesselborg, Sebastian
Guo, Zhiyong
Zou, Kun
Mándi, Attila
Kurtán, Tibor
Liu, Zhen
Proksch, Peter
author_sort Gao, Ying
collection PubMed
description Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO(3) or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC(50) values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.
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spelling pubmed-76720182020-11-26 Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach Gao, Ying Stuhldreier, Fabian Schmitt, Laura Wesselborg, Sebastian Guo, Zhiyong Zou, Kun Mándi, Attila Kurtán, Tibor Liu, Zhen Proksch, Peter Front Microbiol Microbiology Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO(3) or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC(50) values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death. Frontiers Media S.A. 2020-11-04 /pmc/articles/PMC7672018/ /pubmed/33250887 http://dx.doi.org/10.3389/fmicb.2020.600983 Text en Copyright © 2020 Gao, Stuhldreier, Schmitt, Wesselborg, Guo, Zou, Mándi, Kurtán, Liu and Proksch. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Gao, Ying
Stuhldreier, Fabian
Schmitt, Laura
Wesselborg, Sebastian
Guo, Zhiyong
Zou, Kun
Mándi, Attila
Kurtán, Tibor
Liu, Zhen
Proksch, Peter
Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title_full Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title_fullStr Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title_full_unstemmed Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title_short Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
title_sort induction of new lactam derivatives from the endophytic fungus aplosporella javeedii through an osmac approach
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672018/
https://www.ncbi.nlm.nih.gov/pubmed/33250887
http://dx.doi.org/10.3389/fmicb.2020.600983
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