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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Autores principales:	Daniel Männle, Shaun M. K. McKinnie, Shrikant S. Mantri, Katharina Steinke, Zeyin Lu, Bradley S. Moore, Nadine Ziemert, Leonard Kaysser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Nocardia biosynthetic gene cluster genome mining genomics metabolomics natural products Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0ac07598e2634368ad0f8b7ad0b2061e
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spelling	oai:doaj.org-article:0ac07598e2634368ad0f8b7ad0b2061e2021-12-02T19:46:20ZComparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic>10.1128/mSystems.00125-202379-5077https://doaj.org/article/0ac07598e2634368ad0f8b7ad0b2061e2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00125-20https://doaj.org/toc/2379-5077ABSTRACT 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.Daniel MännleShaun M. K. McKinnieShrikant S. MantriKatharina SteinkeZeyin LuBradley S. MooreNadine ZiemertLeonard KaysserAmerican Society for MicrobiologyarticleNocardiabiosynthetic gene clustergenome mininggenomicsmetabolomicsnatural productsMicrobiologyQR1-502ENmSystems, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nocardia biosynthetic gene cluster genome mining genomics metabolomics natural products Microbiology QR1-502
spellingShingle	Nocardia biosynthetic gene cluster genome mining genomics metabolomics natural products Microbiology QR1-502 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>
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.
format	article
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
title	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_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_sort	comparative genomics and metabolomics in the genus <italic toggle="yes">nocardia</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/0ac07598e2634368ad0f8b7ad0b2061e
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Comparative Genomics and Metabolomics in the Genus <italic toggle="yes">Nocardia</italic>

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