Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining
<i>Aspergillus pachycristatus</i> is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism <i>A. nidulans</i>. Its secondary metabolism is largely unknown except for the production of echinocandin B and s...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/4/913 |
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| author | Bruno Perlatti Nan Lan Yongying Jiang Zhiqiang An Gerald Bills |
| author_facet | Bruno Perlatti Nan Lan Yongying Jiang Zhiqiang An Gerald Bills |
| author_sort | Bruno Perlatti |
| collection | DOAJ |
| description | <i>Aspergillus pachycristatus</i> is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism <i>A. nidulans</i>. Its secondary metabolism is largely unknown except for the production of echinocandin B and sterigmatocystin. We constructed mutants for three genes that regulate secondary metabolism in <i>A. pachycristatus</i> NRRL 11440, and evaluated the secondary metabolites produced by wild type and mutants strains. The secondary metabolism was explored by metabolic networking of UPLC-HRMS/MS data. The genes and metabolites of <i>A. pachycristatus</i> were compared to those of <i>A.</i> <i>nidulans</i> FGSC A4 as a reference to identify compounds and link them to their encoding genes. Major differences in chromatographic profiles were observable among the mutants. At least 28 molecules were identified in crude extracts that corresponded to nine characterized gene clusters. Moreover, metabolic networking revealed the presence of a yet unexplored array of secondary metabolites, including several undescribed fellutamides derivatives. Comparative reference to its sister species, <i>A. nidulans</i>, was an efficient way to dereplicate known compounds, whereas metabolic networking provided information that allowed prioritization of unknown compounds for further metabolic exploration. The mutation of global regulator genes proved to be a useful tool for expanding the expression of metabolic diversity in <i>A. pachycristatus</i>. |
| first_indexed | 2024-12-11T20:49:09Z |
| format | Article |
| id | doaj.art-865275b43a2b4ecaa4d3553611ddc9fe |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T20:49:09Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-865275b43a2b4ecaa4d3553611ddc9fe2022-12-22T00:51:16ZengMDPI AGMolecules1420-30492020-02-0125491310.3390/molecules25040913molecules25040913Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome MiningBruno Perlatti0Nan Lan1Yongying Jiang2Zhiqiang An3Gerald Bills4Texas Therapeutic Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USATexas Therapeutic Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USAInstitute for Applied Cancer Science, M.D. Anderson Cancer Center, Houston, TX 77054, USATexas Therapeutic Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USATexas Therapeutic Institute, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77054, USA<i>Aspergillus pachycristatus</i> is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism <i>A. nidulans</i>. Its secondary metabolism is largely unknown except for the production of echinocandin B and sterigmatocystin. We constructed mutants for three genes that regulate secondary metabolism in <i>A. pachycristatus</i> NRRL 11440, and evaluated the secondary metabolites produced by wild type and mutants strains. The secondary metabolism was explored by metabolic networking of UPLC-HRMS/MS data. The genes and metabolites of <i>A. pachycristatus</i> were compared to those of <i>A.</i> <i>nidulans</i> FGSC A4 as a reference to identify compounds and link them to their encoding genes. Major differences in chromatographic profiles were observable among the mutants. At least 28 molecules were identified in crude extracts that corresponded to nine characterized gene clusters. Moreover, metabolic networking revealed the presence of a yet unexplored array of secondary metabolites, including several undescribed fellutamides derivatives. Comparative reference to its sister species, <i>A. nidulans</i>, was an efficient way to dereplicate known compounds, whereas metabolic networking provided information that allowed prioritization of unknown compounds for further metabolic exploration. The mutation of global regulator genes proved to be a useful tool for expanding the expression of metabolic diversity in <i>A. pachycristatus</i>.https://www.mdpi.com/1420-3049/25/4/913<i>aspergillus pachycristatus</i>metabolic networkingglobal regulatorslaeaveamcra |
| spellingShingle | Bruno Perlatti Nan Lan Yongying Jiang Zhiqiang An Gerald Bills Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining Molecules <i>aspergillus pachycristatus</i> metabolic networking global regulators laea vea mcra |
| title | Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining |
| title_full | Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining |
| title_fullStr | Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining |
| title_full_unstemmed | Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining |
| title_short | Identification of Secondary Metabolites from <i>Aspergillus pachycristatus</i> by Untargeted UPLC-ESI-HRMS/MS and Genome Mining |
| title_sort | identification of secondary metabolites from i aspergillus pachycristatus i by untargeted uplc esi hrms ms and genome mining |
| topic | <i>aspergillus pachycristatus</i> metabolic networking global regulators laea vea mcra |
| url | https://www.mdpi.com/1420-3049/25/4/913 |
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