Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes

The present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that the...

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Main Authors: Madhaiyan Munusamy, Kuan Chieh Ching, Lay Kien Yang, Sharon Crasta, Martin Muthee Gakuubi, Zhao Yan Chee, Mario Wibowo, Chung Yan Leong, Yoganathan Kanagasundaram, Siew Bee Ng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Chemistry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2022.1024854/full
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author Madhaiyan Munusamy
Kuan Chieh Ching
Lay Kien Yang
Sharon Crasta
Martin Muthee Gakuubi
Martin Muthee Gakuubi
Zhao Yan Chee
Mario Wibowo
Chung Yan Leong
Yoganathan Kanagasundaram
Siew Bee Ng
author_facet Madhaiyan Munusamy
Kuan Chieh Ching
Lay Kien Yang
Sharon Crasta
Martin Muthee Gakuubi
Martin Muthee Gakuubi
Zhao Yan Chee
Mario Wibowo
Chung Yan Leong
Yoganathan Kanagasundaram
Siew Bee Ng
author_sort Madhaiyan Munusamy
collection DOAJ
description The present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that these isolates belong to 46 morphotypes and are affiliated to 23 different taxa in 17 genera of the Ascomycota phylum. Colletotrichum was the most dominant fungal genus accounting for 37% of all the isolates, followed by Diaporthe (13%), Phyllosticta (10.9%) and Diplodia (8.7%). Chemical elicitation using 5-azacytidine, a DNA methyltransferase inhibitor and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor resulted in an increase in the number of active strains. Bioassay-guided isolation and structural elucidation yielded pestahivin and two new analogues from Bartalinia sp. F9447. Pestahivin and its related analogues did not exhibit antibacterial activity against Staphylococcus aureus but displayed strong antifungal activities against Candida albicans and Aspergillus brasiliensis, with IC50 values ranging from 0.46 ± 0.06 to 144 ± 18 µM. Pestahivin and its two analogues furthermore exhibited cytotoxic activity against A549 and MIA PACA-2 cancer cell lines with IC50 values in the range of 0.65 ± 0.12 to 42 ± 5.2 µM. The finding from this study reinforces that chemical epigenetic induction is a promising approach for the discovery of bioactive fungal secondary metabolites encoded by cryptic gene clusters.
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spelling doaj.art-b2a85d1f748a475e90a57bc2a8b5e09f2022-12-22T03:43:50ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-11-011010.3389/fchem.2022.10248541024854Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytesMadhaiyan Munusamy0Kuan Chieh Ching1Lay Kien Yang2Sharon Crasta3Martin Muthee Gakuubi4Martin Muthee Gakuubi5Zhao Yan Chee6Mario Wibowo7Chung Yan Leong8Yoganathan Kanagasundaram9Siew Bee Ng10Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSchool of Biological Sciences, Nanyang Technological University, Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeThe present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that these isolates belong to 46 morphotypes and are affiliated to 23 different taxa in 17 genera of the Ascomycota phylum. Colletotrichum was the most dominant fungal genus accounting for 37% of all the isolates, followed by Diaporthe (13%), Phyllosticta (10.9%) and Diplodia (8.7%). Chemical elicitation using 5-azacytidine, a DNA methyltransferase inhibitor and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor resulted in an increase in the number of active strains. Bioassay-guided isolation and structural elucidation yielded pestahivin and two new analogues from Bartalinia sp. F9447. Pestahivin and its related analogues did not exhibit antibacterial activity against Staphylococcus aureus but displayed strong antifungal activities against Candida albicans and Aspergillus brasiliensis, with IC50 values ranging from 0.46 ± 0.06 to 144 ± 18 µM. Pestahivin and its two analogues furthermore exhibited cytotoxic activity against A549 and MIA PACA-2 cancer cell lines with IC50 values in the range of 0.65 ± 0.12 to 42 ± 5.2 µM. The finding from this study reinforces that chemical epigenetic induction is a promising approach for the discovery of bioactive fungal secondary metabolites encoded by cryptic gene clusters.https://www.frontiersin.org/articles/10.3389/fchem.2022.1024854/fullBartalinia sp.endophyteschemical elicitorspestahivin analoguesmangrove
spellingShingle Madhaiyan Munusamy
Kuan Chieh Ching
Lay Kien Yang
Sharon Crasta
Martin Muthee Gakuubi
Martin Muthee Gakuubi
Zhao Yan Chee
Mario Wibowo
Chung Yan Leong
Yoganathan Kanagasundaram
Siew Bee Ng
Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
Frontiers in Chemistry
Bartalinia sp.
endophytes
chemical elicitors
pestahivin analogues
mangrove
title Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
title_full Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
title_fullStr Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
title_full_unstemmed Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
title_short Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
title_sort chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
topic Bartalinia sp.
endophytes
chemical elicitors
pestahivin analogues
mangrove
url https://www.frontiersin.org/articles/10.3389/fchem.2022.1024854/full
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AT laykienyang chemicalelicitationasanavenuefordiscoveryofbioactivecompoundsfromfungalendophytes
AT sharoncrasta chemicalelicitationasanavenuefordiscoveryofbioactivecompoundsfromfungalendophytes
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