Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic>
ABSTRACT Using automated genome analysis tools, it is often unclear to what degree genetic variability in homologous biosynthetic pathways relates to structural variation. This hampers strain prioritization and compound identification and can lead to overinterpretation of chemical diversity. Here, w...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-06-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.00125-20 |
| _version_ | 1818461127922679808 |
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| author | Daniel Männle Shaun M. K. McKinnie Shrikant S. Mantri Katharina Steinke Zeyin Lu Bradley S. Moore Nadine Ziemert Leonard Kaysser |
| author_facet | Daniel Männle Shaun M. K. McKinnie Shrikant S. Mantri Katharina Steinke Zeyin Lu Bradley S. Moore Nadine Ziemert Leonard Kaysser |
| author_sort | Daniel Männle |
| collection | DOAJ |
| description | ABSTRACT Using automated genome analysis tools, it is often unclear to what degree genetic variability in homologous biosynthetic pathways relates to structural variation. This hampers strain prioritization and compound identification and can lead to overinterpretation of chemical diversity. Here, we assessed the metabolic potential of Nocardia, an underinvestigated actinobacterial genus that is known to comprise opportunistic human pathogens. Our analysis revealed a plethora of putative biosynthetic gene clusters of various classes, including polyketide, nonribosomal peptide, and terpenoid pathways. Furthermore, we used the highly conserved biosynthetic pathway for nocobactin-like siderophores to investigate how gene cluster differences correlate to structural differences in the produced compounds. Sequence similarity networks generated by BiG-SCAPE (Biosynthetic Gene Similarity Clustering and Prospecting Engine) showed the presence of several distinct gene cluster families. Metabolic profiling of selected Nocardia strains using liquid chromatography-mass spectrometry (LC-MS) metabolomics data, nuclear magnetic resonance (NMR) spectroscopy, and GNPS (Global Natural Product Social molecular networking) revealed that nocobactin-like biosynthetic gene cluster (BGC) families above a BiG-SCAPE threshold of 70% can be assigned to distinct structural types of nocobactin-like siderophores. IMPORTANCE Our work emphasizes that Nocardia represent a prolific source for natural products rivaling better-characterized genera such as Streptomyces or Amycolatopsis. Furthermore, we showed that large-scale analysis of biosynthetic gene clusters using similarity networks with high stringency allows the distinction and prediction of natural product structural variations. This will facilitate future genomics-driven drug discovery campaigns. |
| first_indexed | 2024-12-14T23:41:13Z |
| format | Article |
| id | doaj.art-0ac07598e2634368ad0f8b7ad0b2061e |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-14T23:41:13Z |
| publishDate | 2020-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-0ac07598e2634368ad0f8b7ad0b2061e2022-12-21T22:43:31ZengAmerican Society for MicrobiologymSystems2379-50772020-06-015310.1128/mSystems.00125-20Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic>Daniel Männle0Shaun M. K. McKinnie1Shrikant S. Mantri2Katharina Steinke3Zeyin Lu4Bradley S. Moore5Nadine Ziemert6Leonard Kaysser7Pharmaceutical Biology, Eberhard Karls University Tübingen, Tübingen, GermanyDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, California, USAGerman Centre for Infection Research (DZIF), Tübingen, GermanyGerman Centre for Infection Research (DZIF), Tübingen, GermanyPharmaceutical Biology, Eberhard Karls University Tübingen, Tübingen, GermanyScripps Institution of Oceanography, University of California, San Diego, California, USAGerman Centre for Infection Research (DZIF), Tübingen, GermanyPharmaceutical Biology, Eberhard Karls University Tübingen, Tübingen, GermanyABSTRACT Using automated genome analysis tools, it is often unclear to what degree genetic variability in homologous biosynthetic pathways relates to structural variation. This hampers strain prioritization and compound identification and can lead to overinterpretation of chemical diversity. Here, we assessed the metabolic potential of Nocardia, an underinvestigated actinobacterial genus that is known to comprise opportunistic human pathogens. Our analysis revealed a plethora of putative biosynthetic gene clusters of various classes, including polyketide, nonribosomal peptide, and terpenoid pathways. Furthermore, we used the highly conserved biosynthetic pathway for nocobactin-like siderophores to investigate how gene cluster differences correlate to structural differences in the produced compounds. Sequence similarity networks generated by BiG-SCAPE (Biosynthetic Gene Similarity Clustering and Prospecting Engine) showed the presence of several distinct gene cluster families. Metabolic profiling of selected Nocardia strains using liquid chromatography-mass spectrometry (LC-MS) metabolomics data, nuclear magnetic resonance (NMR) spectroscopy, and GNPS (Global Natural Product Social molecular networking) revealed that nocobactin-like biosynthetic gene cluster (BGC) families above a BiG-SCAPE threshold of 70% can be assigned to distinct structural types of nocobactin-like siderophores. IMPORTANCE Our work emphasizes that Nocardia represent a prolific source for natural products rivaling better-characterized genera such as Streptomyces or Amycolatopsis. Furthermore, we showed that large-scale analysis of biosynthetic gene clusters using similarity networks with high stringency allows the distinction and prediction of natural product structural variations. This will facilitate future genomics-driven drug discovery campaigns.https://journals.asm.org/doi/10.1128/mSystems.00125-20Nocardiabiosynthetic gene clustergenome mininggenomicsmetabolomicsnatural products |
| spellingShingle | Daniel Männle Shaun M. K. McKinnie Shrikant S. Mantri Katharina Steinke Zeyin Lu Bradley S. Moore Nadine Ziemert Leonard Kaysser Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> mSystems Nocardia biosynthetic gene cluster genome mining genomics metabolomics natural products |
| title | Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> |
| title_full | Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> |
| title_fullStr | Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> |
| title_full_unstemmed | Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> |
| title_short | Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic> |
| title_sort | comparative genomics and metabolomics in the genus italic toggle yes nocardia italic |
| topic | Nocardia biosynthetic gene cluster genome mining genomics metabolomics natural products |
| url | https://journals.asm.org/doi/10.1128/mSystems.00125-20 |
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