Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria
Multi-omic approaches have recently made big strides toward the effective exploration of microorganisms, accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the Streptomyces sp. R...
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| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.906161/full |
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| author | Rima Ouchene Rima Ouchene Didier Stien Juliette Segret Mouloud Kecha Alice M. S. Rodrigues Carole Veckerlé Marcelino T. Suzuki |
| author_facet | Rima Ouchene Rima Ouchene Didier Stien Juliette Segret Mouloud Kecha Alice M. S. Rodrigues Carole Veckerlé Marcelino T. Suzuki |
| author_sort | Rima Ouchene |
| collection | DOAJ |
| description | Multi-omic approaches have recently made big strides toward the effective exploration of microorganisms, accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the Streptomyces sp. RO-S4 strain isolated from the polluted waters of Bejaia Bay in Algeria. Antagonistic assays against methicillin-resistant Staphylococcus aureus with RO-S4 organic extracts showed an inhibition zone of 20 mm by using the agar diffusion method, and its minimum inhibitory concentration was 16 μg/ml. A molecular network was created using GNPS and annotated through the comparison of MS/MS spectra against several databases. The predominant compounds in the RO-S4 extract belonged to the angucycline family. Three compounds were annotated as known metabolites, while all the others were putatively new to Science. Notably, all compounds had fridamycin-like aglycones, and several of them had a lactonized D ring analogous to that of urdamycin L. The whole genome of Streptomyces RO-S4 was sequenced to identify the biosynthetic gene cluster (BGC) linked to these angucyclines, which yielded a draft genome of 7,497,846 bp with 72.4% G+C content. Subsequently, a genome mining analysis revealed 19 putative biosynthetic gene clusters, including a grincamycin-like BGC with high similarity to that of Streptomyces sp. CZN-748, that was previously reported to also produce mostly open fridamycin-like aglycones. As the ring-opening process leading to these compounds is still not defined, we performed a comparative analysis with other angucycline BGCs and advanced some hypotheses to explain the ring-opening and lactonization, possibly linked to the uncoupling between the activity of GcnE and GcnM homologs in the RO-S4 strain. The combination of metabolomic and genomic approaches greatly improved the interpretation of the metabolic potential of the RO-S4 strain. |
| first_indexed | 2024-12-12T17:23:53Z |
| format | Article |
| id | doaj.art-a4d4d3f8ec824ed0ba186840214483bd |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T17:23:53Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-a4d4d3f8ec824ed0ba186840214483bd2022-12-22T00:17:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-06-011310.3389/fmicb.2022.906161906161Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, AlgeriaRima Ouchene0Rima Ouchene1Didier Stien2Juliette Segret3Mouloud Kecha4Alice M. S. Rodrigues5Carole Veckerlé6Marcelino T. Suzuki7Laboratoire de Microbiologie Appliquée (LMA), Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia, AlgeriaSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceLaboratoire de Microbiologie Appliquée (LMA), Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia, AlgeriaSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceSorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes, LBBM, F-66650, Banyuls-sur-mer, FranceMulti-omic approaches have recently made big strides toward the effective exploration of microorganisms, accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the Streptomyces sp. RO-S4 strain isolated from the polluted waters of Bejaia Bay in Algeria. Antagonistic assays against methicillin-resistant Staphylococcus aureus with RO-S4 organic extracts showed an inhibition zone of 20 mm by using the agar diffusion method, and its minimum inhibitory concentration was 16 μg/ml. A molecular network was created using GNPS and annotated through the comparison of MS/MS spectra against several databases. The predominant compounds in the RO-S4 extract belonged to the angucycline family. Three compounds were annotated as known metabolites, while all the others were putatively new to Science. Notably, all compounds had fridamycin-like aglycones, and several of them had a lactonized D ring analogous to that of urdamycin L. The whole genome of Streptomyces RO-S4 was sequenced to identify the biosynthetic gene cluster (BGC) linked to these angucyclines, which yielded a draft genome of 7,497,846 bp with 72.4% G+C content. Subsequently, a genome mining analysis revealed 19 putative biosynthetic gene clusters, including a grincamycin-like BGC with high similarity to that of Streptomyces sp. CZN-748, that was previously reported to also produce mostly open fridamycin-like aglycones. As the ring-opening process leading to these compounds is still not defined, we performed a comparative analysis with other angucycline BGCs and advanced some hypotheses to explain the ring-opening and lactonization, possibly linked to the uncoupling between the activity of GcnE and GcnM homologs in the RO-S4 strain. The combination of metabolomic and genomic approaches greatly improved the interpretation of the metabolic potential of the RO-S4 strain.https://www.frontiersin.org/articles/10.3389/fmicb.2022.906161/fullmarine Streptomycesantibacterial activityMRSAmetabolomic analysismolecular networkinggenome mining |
| spellingShingle | Rima Ouchene Rima Ouchene Didier Stien Juliette Segret Mouloud Kecha Alice M. S. Rodrigues Carole Veckerlé Marcelino T. Suzuki Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria Frontiers in Microbiology marine Streptomyces antibacterial activity MRSA metabolomic analysis molecular networking genome mining |
| title | Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria |
| title_full | Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria |
| title_fullStr | Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria |
| title_full_unstemmed | Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria |
| title_short | Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria |
| title_sort | integrated metabolomic molecular networking and genome mining analyses uncover novel angucyclines from streptomyces sp ro s4 strain isolated from bejaia bay algeria |
| topic | marine Streptomyces antibacterial activity MRSA metabolomic analysis molecular networking genome mining |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.906161/full |
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