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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2021
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ftcdlib:oai:escholarship.org:ark:/13030/qt4rk7f1fm 2023-11-12T04:06:33+01:00 Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential Murray, Alison E Lo, Chien-Chi Daligault, Hajnalka E Avalon, Nicole E Read, Robert W Davenport, Karen W Higham, Mary L Kunde, Yuliya Dichosa, Armand EK Baker, Bill J Chain, Patrick SG Campbell, Barbara J e00759 - e00721 2021-12-22 application/pdf https://escholarship.org/uc/item/4rk7f1fm unknown eScholarship, University of California qt4rk7f1fm https://escholarship.org/uc/item/4rk7f1fm public mSphere, vol 6, iss 6 Microbiology Biological Sciences Biotechnology Genetics Human Genome Animals Antarctic Regions Macrolides Microbiota Multigene Family Phylogeny RNA Ribosomal 16S Urochordata Verrucomicrobia Antarctic Synoicihabitans palmerolidicus Synoicum adareanum anticancer ascidian natural product biosynthetic gene cluster microbiome metagenome palmerolide secondary metabolite article 2021 ftcdlib 2023-10-16T18:04:50Z 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. IMPORTANCE Palmerolide A has potential as a chemotherapeutic agent to target melanoma. We interrogated the microbiome of the Antarctic ascidian, Synoicum adareanum, ... Article in Journal/Newspaper Antarc* Antarctic University of California: eScholarship Antarctic The Antarctic |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Microbiology Biological Sciences Biotechnology Genetics Human Genome Animals Antarctic Regions Macrolides Microbiota Multigene Family Phylogeny RNA Ribosomal 16S Urochordata Verrucomicrobia Antarctic Synoicihabitans palmerolidicus Synoicum adareanum anticancer ascidian natural product biosynthetic gene cluster microbiome metagenome palmerolide secondary metabolite |
spellingShingle |
Microbiology Biological Sciences Biotechnology Genetics Human Genome Animals Antarctic Regions Macrolides Microbiota Multigene Family Phylogeny RNA Ribosomal 16S Urochordata Verrucomicrobia Antarctic Synoicihabitans palmerolidicus Synoicum adareanum anticancer ascidian natural product biosynthetic gene cluster microbiome metagenome palmerolide secondary metabolite Murray, Alison E Lo, Chien-Chi Daligault, Hajnalka E Avalon, Nicole E Read, Robert W Davenport, Karen W Higham, Mary L Kunde, Yuliya Dichosa, Armand EK Baker, Bill J Chain, Patrick SG Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential |
topic_facet |
Microbiology Biological Sciences Biotechnology Genetics Human Genome Animals Antarctic Regions Macrolides Microbiota Multigene Family Phylogeny RNA Ribosomal 16S Urochordata Verrucomicrobia Antarctic Synoicihabitans palmerolidicus Synoicum adareanum anticancer ascidian natural product biosynthetic gene cluster microbiome metagenome palmerolide secondary metabolite |
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. IMPORTANCE Palmerolide A has potential as a chemotherapeutic agent to target melanoma. We interrogated the microbiome of the Antarctic ascidian, Synoicum adareanum, ... |
author2 |
Campbell, Barbara J |
format |
Article in Journal/Newspaper |
author |
Murray, Alison E Lo, Chien-Chi Daligault, Hajnalka E Avalon, Nicole E Read, Robert W Davenport, Karen W Higham, Mary L Kunde, Yuliya Dichosa, Armand EK Baker, Bill J Chain, Patrick SG |
author_facet |
Murray, Alison E Lo, Chien-Chi Daligault, Hajnalka E Avalon, Nicole E Read, Robert W Davenport, Karen W Higham, Mary L Kunde, Yuliya Dichosa, Armand EK Baker, Bill J Chain, Patrick SG |
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 |
publisher |
eScholarship, University of California |
publishDate |
2021 |
url |
https://escholarship.org/uc/item/4rk7f1fm |
op_coverage |
e00759 - e00721 |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
mSphere, vol 6, iss 6 |
op_relation |
qt4rk7f1fm https://escholarship.org/uc/item/4rk7f1fm |
op_rights |
public |
_version_ |
1782327651995746304 |