Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential
The Antarctic marine ecosystem harbors a wealth of biological and chemical innovation that has risen in concert over millennia since the isolation of the continent and formation of the Antarctic circumpolar current. Scientific inquiry into the novelty of marine natural products produced by Antarctic...
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ftosti:oai:osti.gov:1968220 2023-07-30T03:57:33+02:00 Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential Murray, Alison E. Lo, Chien-Chi Daligault, Hajnalka Erzsebet Avalon, Nicole E. Read, Robert W. Davenport, Karen Walston Higham, Mary L. Kunde, Yuliya A. Dichosa, Armand Earl Ko Baker, Bill J. Chain, Patrick Sam Guy 2023-04-24 application/pdf http://www.osti.gov/servlets/purl/1968220 https://www.osti.gov/biblio/1968220 https://doi.org/10.1128/msphere.00759-21 unknown http://www.osti.gov/servlets/purl/1968220 https://www.osti.gov/biblio/1968220 https://doi.org/10.1128/msphere.00759-21 doi:10.1128/msphere.00759-21 59 BASIC BIOLOGICAL SCIENCES 2023 ftosti https://doi.org/10.1128/msphere.00759-21 2023-07-11T10:26:19Z The Antarctic marine ecosystem harbors a wealth of biological and chemical innovation that has risen in concert over millennia since the isolation of the continent and formation of the Antarctic circumpolar current. Scientific inquiry into the novelty of marine natural products produced by Antarctic benthic invertebrates led to the discovery of a bioactive macrolide, palmerolide A, that has specific activity against melanoma and holds considerable promise as an anticancer therapeutic. While this compound was isolated from the Antarctic ascidian Synoicum adareanum, its biosynthesis has since been hypothesized to be microbially mediated, given structural similarities to microbially produced hybrid nonribosomal peptide-polyketide macrolides. Here, we describe a metagenome-enabled investigation aimed at identifying the biosynthetic gene cluster (BGC) and palmerolide A-producing organism. A 74-kbp candidate BGC encoding the multimodular enzymatic machinery (hybrid type I-trans-AT polyketide synthase-nonribosomal peptide synthetase and tailoring functional domains) was identified and found to harbor key features predicted as necessary for palmerolide A biosynthesis. Surveys of ascidian microbiome samples targeting the candidate BGC revealed a high correlation between palmerolide gene targets and a single 16S rRNA gene variant (R = 0.83 to 0.99). Through repeated rounds of metagenome sequencing followed by binning contigs into metagenome-assembled genomes, we were able to retrieve a nearly complete genome (10 contigs) of the BGC-producing organism, a novel verrucomicrobium within the Opitutaceae family that we propose here as “Candidatus Synoicihabitans palmerolidicus.” The refined genome assembly harbors five highly similar BGC copies, along with structural and functional features that shed light on the host-associated nature of this unique bacterium. Other/Unknown Material Antarc* Antarctic SciTec Connect (Office of Scientific and Technical Information - OSTI, U.S. Department of Energy) Antarctic The Antarctic mSphere 6 6 |
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SciTec Connect (Office of Scientific and Technical Information - OSTI, U.S. Department of Energy) |
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ftosti |
language |
unknown |
topic |
59 BASIC BIOLOGICAL SCIENCES |
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59 BASIC BIOLOGICAL SCIENCES Murray, Alison E. Lo, Chien-Chi Daligault, Hajnalka Erzsebet Avalon, Nicole E. Read, Robert W. Davenport, Karen Walston Higham, Mary L. Kunde, Yuliya A. Dichosa, Armand Earl Ko Baker, Bill J. Chain, Patrick Sam Guy Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
topic_facet |
59 BASIC BIOLOGICAL SCIENCES |
description |
The Antarctic marine ecosystem harbors a wealth of biological and chemical innovation that has risen in concert over millennia since the isolation of the continent and formation of the Antarctic circumpolar current. Scientific inquiry into the novelty of marine natural products produced by Antarctic benthic invertebrates led to the discovery of a bioactive macrolide, palmerolide A, that has specific activity against melanoma and holds considerable promise as an anticancer therapeutic. While this compound was isolated from the Antarctic ascidian Synoicum adareanum, its biosynthesis has since been hypothesized to be microbially mediated, given structural similarities to microbially produced hybrid nonribosomal peptide-polyketide macrolides. Here, we describe a metagenome-enabled investigation aimed at identifying the biosynthetic gene cluster (BGC) and palmerolide A-producing organism. A 74-kbp candidate BGC encoding the multimodular enzymatic machinery (hybrid type I-trans-AT polyketide synthase-nonribosomal peptide synthetase and tailoring functional domains) was identified and found to harbor key features predicted as necessary for palmerolide A biosynthesis. Surveys of ascidian microbiome samples targeting the candidate BGC revealed a high correlation between palmerolide gene targets and a single 16S rRNA gene variant (R = 0.83 to 0.99). Through repeated rounds of metagenome sequencing followed by binning contigs into metagenome-assembled genomes, we were able to retrieve a nearly complete genome (10 contigs) of the BGC-producing organism, a novel verrucomicrobium within the Opitutaceae family that we propose here as “Candidatus Synoicihabitans palmerolidicus.” The refined genome assembly harbors five highly similar BGC copies, along with structural and functional features that shed light on the host-associated nature of this unique bacterium. |
author |
Murray, Alison E. Lo, Chien-Chi Daligault, Hajnalka Erzsebet Avalon, Nicole E. Read, Robert W. Davenport, Karen Walston Higham, Mary L. Kunde, Yuliya A. Dichosa, Armand Earl Ko Baker, Bill J. Chain, Patrick Sam Guy |
author_facet |
Murray, Alison E. Lo, Chien-Chi Daligault, Hajnalka Erzsebet Avalon, Nicole E. Read, Robert W. Davenport, Karen Walston Higham, Mary L. Kunde, Yuliya A. Dichosa, Armand Earl Ko Baker, Bill J. Chain, Patrick Sam Guy |
author_sort |
Murray, Alison E. |
title |
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
title_short |
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
title_full |
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
title_fullStr |
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
title_full_unstemmed |
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
title_sort |
discovery of an antarctic ascidian-associated uncultivated verrucomicrobia with antimelanoma palmerolide biosynthetic potential |
publishDate |
2023 |
url |
http://www.osti.gov/servlets/purl/1968220 https://www.osti.gov/biblio/1968220 https://doi.org/10.1128/msphere.00759-21 |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_relation |
http://www.osti.gov/servlets/purl/1968220 https://www.osti.gov/biblio/1968220 https://doi.org/10.1128/msphere.00759-21 doi:10.1128/msphere.00759-21 |
op_doi |
https://doi.org/10.1128/msphere.00759-21 |
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mSphere |
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6 |
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6 |
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1772817982500634624 |