Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i>
Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most pr...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/16/9055 |
_version_ | 1797523515734228992 |
---|---|
author | Fortunato Palma Esposito Rosa Giugliano Gerardo Della Sala Giovanni Andrea Vitale Carmine Buonocore Janardhan Ausuri Christian Galasso Daniela Coppola Gianluigi Franci Massimiliano Galdiero Donatella de Pascale |
author_facet | Fortunato Palma Esposito Rosa Giugliano Gerardo Della Sala Giovanni Andrea Vitale Carmine Buonocore Janardhan Ausuri Christian Galasso Daniela Coppola Gianluigi Franci Massimiliano Galdiero Donatella de Pascale |
author_sort | Fortunato Palma Esposito |
collection | DOAJ |
description | Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate <i>Rhodococcus</i> sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry. |
first_indexed | 2024-03-10T08:44:05Z |
format | Article |
id | doaj.art-9e0b14b2c4de404cbde4de53bb5f0ae6 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T08:44:05Z |
publishDate | 2021-08-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-9e0b14b2c4de404cbde4de53bb5f0ae62023-11-22T08:04:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216905510.3390/ijms22169055Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i>Fortunato Palma Esposito0Rosa Giugliano1Gerardo Della Sala2Giovanni Andrea Vitale3Carmine Buonocore4Janardhan Ausuri5Christian Galasso6Daniela Coppola7Gianluigi Franci8Massimiliano Galdiero9Donatella de Pascale10Department of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, 80131 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Marine Biotechnology Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, ItalyNatural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate <i>Rhodococcus</i> sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.https://www.mdpi.com/1422-0067/22/16/9055trehalolipidsglycolipidsantiviralantiproliferativebiosurfactantmarine bacteria |
spellingShingle | Fortunato Palma Esposito Rosa Giugliano Gerardo Della Sala Giovanni Andrea Vitale Carmine Buonocore Janardhan Ausuri Christian Galasso Daniela Coppola Gianluigi Franci Massimiliano Galdiero Donatella de Pascale Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> International Journal of Molecular Sciences trehalolipids glycolipids antiviral antiproliferative biosurfactant marine bacteria |
title | Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> |
title_full | Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> |
title_fullStr | Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> |
title_full_unstemmed | Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> |
title_short | Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine <i>Rhodococcus</i> |
title_sort | combining osmac approach and untargeted metabolomics for the identification of new glycolipids with potent antiviral activity produced by a marine i rhodococcus i |
topic | trehalolipids glycolipids antiviral antiproliferative biosurfactant marine bacteria |
url | https://www.mdpi.com/1422-0067/22/16/9055 |
work_keys_str_mv | AT fortunatopalmaesposito combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT rosagiugliano combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT gerardodellasala combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT giovanniandreavitale combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT carminebuonocore combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT janardhanausuri combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT christiangalasso combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT danielacoppola combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT gianluigifranci combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT massimilianogaldiero combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi AT donatelladepascale combiningosmacapproachanduntargetedmetabolomicsfortheidentificationofnewglycolipidswithpotentantiviralactivityproducedbyamarineirhodococcusi |