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</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="34050176">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1038/s41467-021-23502-4"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3094&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=34050176&amp;db=pubmed&amp;nlmid=101528555"
title="See full text options at Nature Publishing Group"
data-ga-category="full_text"
data-ga-action="Nature Publishing Group"
data-ga-label="34050176"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="Nature Publishing Group full text link"><span class="text">
Nature Publishing Group
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/34050176/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=34050176&amp;db=pubmed&amp;nlmid=101528555"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="34050176"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/34050176/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/34050176/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="34050176" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F34050176%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="1vNZVMHAikVZnpA6L9VdFAF6gjiVheztiix4yCaWSVIthQGWosyf9IbKOn07aP7N"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
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Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery
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><sup class="key">9</sup> Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="full-view-affiliation-10"
id="full-view-affiliation-10"
><sup class="key">10</sup> Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt &amp; Senckenberg Research Institute, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="full-view-affiliation-11"
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><sup class="key">11</sup> Max-Planck-Institute for Terrestrial Microbiology, Department for Natural Products in Organismic Interactions, Marburg, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="full-view-affiliation-12"
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><sup class="key">12</sup> Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. ppevzner@ucsd.edu.</li>
<li data-affiliation-id="full-view-affiliation-13"
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><sup class="key">13</sup> Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. hoseinm@andrew.cmu.edu.</li>
</ul>
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<div class="equal-contrib-explanation" id="full-view-equal-contrib-explanation"><sup class="key">#</sup> Contributed equally.</div>
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Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery
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<span class="authors-list-item "><span class="full-name">Bahar Behsaz</span><span class="citation-separator">&nbsp;et al.</span></span>
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Authors
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<span class="authors-list-item "><a class="full-name"
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data-ga-label="Bahar Behsaz">Bahar Behsaz</a><sup class="equal-contrib-container"><span class="author-sup-separator">&nbsp;</span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Center for Microbiome Innovation, University of California at San Diego, La Jolla, CA, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Edna Bode">Edna Bode</a><sup class="equal-contrib-container"><span class="author-sup-separator">&nbsp;</span><a class="equal-contrib" title="Contributed equally" href="#short-view-equal-contrib-explanation" ref="linksrc=author_equal_contrib">#</a></sup><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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5
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Annabell Linck">Annabell Linck</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Changhui Guan">Changhui Guan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Jackson Laboratory of Medical Genomics, Farmington, CT, USA." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Julia Oh">Julia Oh</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Jackson Laboratory of Medical Genomics, Farmington, CT, USA." href="#short-view-affiliation-8" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Pieter C Dorrestein">Pieter C Dorrestein</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Center for Microbiome Innovation, University of California at San Diego, La Jolla, CA, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Helge B Bode">Helge B Bode</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt &amp; Senckenberg Research Institute, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de." href="#short-view-affiliation-10" ref="linksrc=author_aff">
10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Max-Planck-Institute for Terrestrial Microbiology, Department for Natural Products in Organismic Interactions, Marburg, Germany. helge.bode@mpi-marburg.mpg.de." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Pavel A Pevzner">Pavel A Pevzner</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. ppevzner@ucsd.edu." href="#short-view-affiliation-12" ref="linksrc=author_aff">
12
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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13
</a></sup></span>
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</h3>
<ul class="item-list">
<li data-affiliation-id="short-view-affiliation-1"
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><sup class="key">1</sup> Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, USA.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Center for Microbiome Innovation, University of California at San Diego, La Jolla, CA, USA.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St Petersburg, Russia.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Tiny Earth Chemistry Hub, University of Wisconsin-Madison, Madison, WI, USA.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> The Jackson Laboratory of Medical Genomics, Farmington, CT, USA.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Molecular Biotechnology, Department of Biosciences, Goethe University Frankfurt, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt &amp; Senckenberg Research Institute, Frankfurt am Main, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Max-Planck-Institute for Terrestrial Microbiology, Department for Natural Products in Organismic Interactions, Marburg, Germany. helge.bode@mpi-marburg.mpg.de.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. ppevzner@ucsd.edu.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. hoseinm@andrew.cmu.edu.</li>
</ul>
</div>
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<div class="equal-contrib-explanation" id="short-view-equal-contrib-explanation"><sup class="key">#</sup> Contributed equally.</div>
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Publisher Correction: Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery.
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<span class="docsum-authors full-authors">Behsaz B, Bode E, Gurevich A, Shi YN, Grundmann F, Acharya D, Caraballo-Rodríguez AM, Bouslimani A, Panitchpakdi M, Linck A, Guan C, Oh J, Dorrestein PC, Bode HB, Pevzner PA, Mohimani H.</span>
<span class="docsum-authors short-authors">Behsaz B, et al.</span>
<span class="docsum-journal-citation full-journal-citation">Nat Commun. 2021 Jul 8;12(1):4318. doi: 10.1038/s41467-021-24441-w.</span>
<span class="docsum-journal-citation short-journal-citation">Nat Commun. 2021.</span>
<span class="citation-part">PMID: <span class="docsum-pmid">34238936</span></span>
<span class="free-resources spaced-citation-item citation-part">Free PMC article.</span>
<span class="no-abstract spaced-citation-item citation-part">No abstract available.</span>
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Abstract
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<p>
Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, a modification-tolerant tool for NRP discovery from large (meta)genomic and mass spectrometry datasets. We show that NRPminer is able to identify many NRPs from different environments, including four previously unreported NRP families from soil-associated microbes and NRPs from human microbiota. Furthermore, in this work we demonstrate the anti-parasitic activities and the structure of two of these NRP families using direct bioactivity screening and nuclear magnetic resonance spectrometry, illustrating the power of NRPminer for discovering bioactive NRPs.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">P.A.P. is a co-founder, has an equity interest and receives income from Digital Proteomics, LLC. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. B.B. and H.M. are co-founders and have equity interests from Chemia.ai, LLC. The remaining authors declare no competing interests.</p>
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Figures
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<p> Fig. 1. NRPminer pipeline. </p>
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<div class="figure-caption-contents"><b> a </b> Predicting NRPS…</div>
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<p> Fig. 1. NRPminer pipeline. </p>
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<div class="figure-caption-contents"><b> a </b> Predicting NRPS BGCs using antiSMASH. Each ORF is represented by…</div>
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Fig. 1. NRPminer pipeline.
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<div class="figure-caption-contents"><b>a</b> Predicting NRPS BGCs using antiSMASH. Each ORF is represented by an arrow, and each A-domain is represented by a square, <b>b</b> predicting putative amino acids for each NRP residue using NRPSpredictor2 (ref. ), colored circles represents different amino acids (AAs), <b>c</b> generating multiple assembly lines by considering various combinations of ORFs and generating all putative core NRPs for each assembly line in the identified BGC (for brevity only assembly lines generated by deleting a single NRPS unit are shown; in practice, NRPminer considers loss of up to two NRPS units, as well as single and double duplication of each NRPS unit), <b>d</b> filtering the core NRPs based on their specificity scores, <b>e</b> identifying domains corresponding to known modifications and incorporating them in the selected core NRPs (modified amino acids are represented by purple squares), <b>f</b> generating linear, cyclic and branch-cyclic backbone structures for each core NRP, <b>g</b> generating a set of high-scoring PSMs using modification-tolerant VarQuest search of spectra against the database of the constructed putative NRP structures. NRPminer considers all possible mature NRPs with up to one PAM (shown as hexagons) in each NRP structure. For brevity some of the structures are not shown. <b>h</b> Computing statistical significance of PSMs and reporting the significant PSMs, and <b>i</b> expanding the set of identified spectra using spectral networks. Nodes in the spectral network represent spectra and edges connect “similar” spectra (see “Methods”).</div>
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<p> Fig. 2. Spectral networks for nine known… </p>
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<p> Fig. 2. Spectral networks for nine known and three previously unreported NRP families identified by… </p>
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Fig. 2. Spectral networks for nine known and three previously unreported NRP families identified by NRPminer in the XPF dataset.
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<div class="figure-caption-contents">Each node represents a spectrum. The spectra of known NRPs (as identified by spectral library search against the library of all known compounds in GNPS) are shown with a dark blue border. A node is colored if the corresponding spectrum forms a statistically significant PSM and not colored otherwise. We distinguish between identified spectra of known NRPs with known BGCs (colored by light blue) and identified spectra of known NRPs (from xentrivalpeptide family) with previously unknown BGC (colored by dark green). Identified spectra of previously unreported NRPs from known NRP families (previously unreported NRP variants) are colored in light green. Identified spectra of NRPs from previously unreported NRP families are colored in magenta. Proteogomycins and xenoinformycin subnetworks represent previously unreported NRP families. The Xenoamicin-like subnetwork revealed a BGC family distantly related to xenoamicins (6 out 13 amino acids are identical). For simplicity only spectra at charge state +1 are used for the analysis.</div>
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<p> Fig. 3. Identifying protegomycin (PRT) NRP family. </p>
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<p> Fig. 3. Identifying protegomycin (PRT) NRP family. </p>
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<div class="figure-caption-contents"><b> a </b> The BGCs generating the NRP in <i> X.… </i></div>
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Fig. 3. Identifying protegomycin (PRT) NRP family.
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<div class="figure-caption-contents"><b>a</b> The BGCs generating the NRP in <i>X. doucetiae</i> (top) and <i>X. porinarii</i> (bottom) along with NRPS genes (shown in red) and A-, C-, PCP-, and E-domains in these NRPSs. The rest of the genes in the corresponding contigs is shown in white. No BGC was found in <i>Xenorhabdus</i> sp. 30TX1. Three highest-scoring amino acids for each A-domain in these BGCs (according to NRPSpredictor2 (ref. ) predictions) are shown below the corresponding A-domains. Amino acids appearing in the NRPs [+99.06]FYYYYW and [+99.06]FYYYW identified by NRPminer (with the lowest <i>p</i> value) are shown in blue. <b>b</b> Spectral network formed by the spectra that originate from NRPs in the protegomycin family. <b>c</b> Sequences of the identified NRPs in the protegomycin family (with the lowest <i>p</i> value among all spectra originating from the same NRP). PRT represents protegomycin. For MS details see Supplementary Table 3. The <i>p</i> values are computed based on MCMC approach using MS-DPR with 10,000 simulations. <b>d</b> For each strain, an annotated spectrum representing the lowest <i>p</i> value is shown. The spectra were annotated based on predicted NRPs [+99.06]FYYWYW, [+99.06]FYYYYW, and [+99.06]FYYYW from top to bottom. The “+” sign represents the addition of [+99.06Da]. Colors in parts <b>b</b> and <b>d</b> are coordinated. Supplementary Figures 68 show the annotated spectra for all NRPs shown in part (<b>c</b>). <b>e</b> Key HMBC and HSQC-COSY correlations in PRT-1037. <b>f</b> Structures for selected PRT derivatives produced by <i>X. doucetiae</i> including amino acid configuration as concluded from the presence of epimerization domains in the corresponding NRPSs and acyl residues as concluded from feeding experiments (Supplementary Fig. 9). Predicted structures for all identified PRT derivatives from <i>X. doucetiae</i>, <i>X. poinarii</i>, and 30TX1 are shown in Supplementary Figs. 10 and S11.</div>
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<p> Fig. 4. Identifying xenoinformycin (XINF) NRP family. </p>
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<p> Fig. 4. Identifying xenoinformycin (XINF) NRP family. </p>
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<div class="figure-caption-contents"><b> a </b> The BGC generating the NRP in <i> X.… </i></div>
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Fig. 4. Identifying xenoinformycin (XINF) NRP family.
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<div class="figure-caption-contents"><b>a</b> The BGC generating the NRP in <i>X. miraniensis</i> along with NRPS genes (shown in red) and the A-, C-, PCP-, and C/E-domains appearing on the corresponding NRPS. The rest of the genes in the corresponding contigs are shown in white. Three highest-scoring amino acids for each A-domain in this BGC (according to NRPSpredictor2 (ref. ) predictions) are shown below the corresponding A-domains. Amino acids appearing in the NRP VVWFF identified by NRPminer (with the lowest <i>p</i> value) are shown in blue. <b>b</b> Spectral network formed by the spectra that originate from NRPs in the xenoinformycin family. A node is colored if the corresponding spectrum forms a statistically significant PSM (with <i>p</i> value threshold 10<sup>15</sup>) and not colored otherwise. <b>c</b> Sequences of the identified NRPs in the xenoinformycin family (with the lowest <i>p</i> value among all spectra originating from the same NRP). XINF represents xenoinformycin. The <i>p</i> values are computed based on MCMC approach using MS-DPR with 10,000 simulations. <b>d</b> For each identified NRP, an annotated spectrum forming a PSM with the lowest <i>p</i> value is shown.</div>
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<p> Fig. 5. Identifying xenoamicin-like (XAM) NRP family. </p>
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<p> Fig. 5. Identifying xenoamicin-like (XAM) NRP family. </p>
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<div class="figure-caption-contents"><b> a </b> The BGCs generating the NRP in <i> Xenorhabdus… </i></div>
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Fig. 5. Identifying xenoamicin-like (XAM) NRP family.
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<div class="figure-caption-contents"><b>a</b> The BGCs generating the NRP in <i>Xenorhabdus</i> sp. KJ12 along with NRPS genes (shown in red) and A-, C-, PCP-, and E-domains in these NRPSs. The rest of the genes in the corresponding contigs are shown in white. Three highest-scoring amino acids for each A-domain in these BGCs (according to NRPSpredictor2 (ref. ) predictions) are shown below the corresponding A-domains. Amino acids appearing in the NRP [+99.06]TAVLLTTLLAAPA identified by NRPminer (with the lowest <i>p</i> value) are shown in blue. <b>b</b> Spectral network formed by the spectra that originate from NRPs in the XAM family. <b>c</b> Sequences of the identified NRPs in this family (with the lowest <i>p</i> value among all spectra originating from the same NRP). The <i>p</i> values are computed based on MCMC approach using MS-DPR with 10,000 simulations. <b>d</b> For each strain, an annotated spectrum representing the lowest <i>p</i> value is shown. The spectra were annotated based on predicted NRPs [+99.06]TAVLLTTLLAAPA and [+99.06] TAVLLTTLVAAPA from top to bottom. The “+” sign represents the addition of [+99.06]. Supplementary Figures 23 and S24 show the annotated spectra for the other NRPs shown in part (<b>c</b>). <b>e</b> NMR-based correlations of XAM-1320 (<i>m</i>/<i>z</i> 1320.8 [M+H]<sup>+</sup>) produced by <i>Xenorhabdus</i> KJ12.1 (Supplementary Table 5 and Supplementary Figs. 2529). HSQC-TOCSY (bold lines) and key ROESY correlations (arrows) are shown. <b>f</b> 3D structure of XAM-1320 derived from 121 ROE-derived distance constraints (Supplementary Table 6), molecular dynamics, and energy minimization. Peptide backbone is visualized with a yellow bar (left). Predicted hydrogen bonds stabilizing the β-helix are shown as dashed lines. View from above at the pore formed by XAM-1320 (right). NRPminer identified this NRP with <i>p</i> value 8.4×10<sup>50</sup>.</div>
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<p> Fig. 6. Identifying aminformatide (AMINF) NRP family… </p>
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<p> Fig. 6. Identifying aminformatide (AMINF) NRP family discovered by NRPminer in the <i> SoilActi </i> dataset. </p>
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Fig. 6. Identifying aminformatide (AMINF) NRP family discovered by NRPminer in the <i>SoilActi</i> dataset.
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<div class="figure-caption-contents"><b>a</b> The BGC generating the core NRP in <i>Amycolatopsis</i> sp. AA4 along with NRPS genes (shown in red) and the A-, C-, PCP, and E-domains appearing in the corresponding NRPS. The rest of the genes in the corresponding contigs are shown in white. Three highest-scoring amino acids for each A-domain in this BGC (according to NRPSpredictor2 (ref. ) predictions) are shown below the corresponding A-domains. Amino acids appearing in the NRP VVIVETRY identified by NRPminer (with the lowest <i>p</i> value) are shown in blue. <b>b</b> Spectral network formed by spectra that originate from the AMINF NRPs. A node is colored if the corresponding spectrum forms a statistically significant PSM and not colored otherwise. The <i>p</i> values are computed based on MCMC approach using MS-DPR with 10,000 simulations. <b>c</b> Sequences of the NRPs identified by NRPminer in the aminformatide family (with the lowest <i>p</i> value among all PSMs originating from the same NRP). NRPminer predicted a PAM with loss of ~0.96Da on E, represented by E*. AMINF represents aminformatide. <b>d</b> For each identified NRP, an annotated spectrum representing the lowest <i>p</i> value is shown.</div>
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<p> Fig. 7. Lugdunin BGC and the assembly lines formed by NRPminer using the OrfDup option. </p>
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Fig. 7. Lugdunin BGC and the assembly lines formed by NRPminer using the OrfDup option.
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<div class="figure-caption-contents"><b>a</b> Lugdunin BGC with the four ORFs shown in different colors. The squares represent the A-domains. <b>b</b> Assembly lines formed by duplication of a single NRPS subunit (corresponding to each ORF) zero, one, and two times are pictured. NRPminer explores all assembly lines generated by duplicating each ORF up to two times when the “OrfDup” option is selected. <b>c</b> The NRPS assembly lined (with A-, C-, PCP-, and E-domains pictured) appearing in the NRPS that synthesizes lugdunin, where one Val-specific A-domain loads three amino acids (<i>valines</i>) to the growing peptide. Amino acids corresponding to lugdunin structure are shown below each A-domain. Circles represent amino acids (different amino acids are shown by different colors). <b>d</b> Cyclic structure of lugdunin with the amino acids highlighted in blue. The “Cys*” represent Cys-derived thiazolidine in lugdunin structure.</div>
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<p> Fig. 8. Arthrofactin (ARF) NRP family. </p>
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<p> Fig. 8. Arthrofactin (ARF) NRP family. </p>
</strong>
<div class="figure-caption-contents"><b> a </b> The BGCs generating the NRP in <i> Pseudomonas baetica… </i></div>
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<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Fig. 8. Arthrofactin (ARF) NRP family.
</strong>
<div class="figure-caption-contents"><b>a</b> The BGCs generating the NRP in <i>Pseudomonas baetica</i> sp. 04-6(1) along with the NRPS genes (shown in red) and A-, C-, C/E-, PCP-, and E-domains in these NRPSs. The rest of the genes in the corresponding contigs are shown in white. Three highest-scoring amino acids for each A-domain in these BGCs (according to NRPSpredictor2 (ref. ) predictions) are shown below the corresponding A-domains. Amino acids appearing in the known NRP ARF-1354 with amino acid sequence [+170.13]LDTLLSLSILD are shown in blue. <b>b</b> Spectral network formed by the spectra that originate from NRPs in the ARF family. The known arthrofactins are shown in blue, while the purples nodes represent the previously unreported variants identified by NRPminer. All identified athrofactins share the same core NRP LDTLLSLSILD. <b>c</b> Sequences of the identified NRPs in this family (with the lowest <i>p</i> value among all spectra originating from the same NRP). Column “structure” shows if the predicted structure for the identified NRPs is linear or branch-cyclic (shown by b-cyclic). The <i>p</i> values are computed based on MCMC approach using MS-DPR with 10,000 simulations. <b>d</b> Two annotated spectra representing the PSMs (with the lowest <i>p</i> values among spectra originating from the same NRPs) corresponding to ARF-1354 and 1326. The two spectra were annotated based on predicted NRPs [+170.13]LDTLLSLSILD (PSM <i>p</i> value 2.7×10<sup>39</sup>) and [+142.11]LDTLLSLSILD (PSM <i>p</i> value 6.5 <math><mo>&#215;</mo></math> 10<sup>55</sup>), from top to bottom. The “+” and “*” signs represent the addition of [+170.13] and [+142.11], respectively. <b>e</b> The 2D structure of known arthrofactin ARF-1354 (ref. ). NRPminer identified this NRP with <i>p</i> value 2.7×10<sup>39</sup>.</div>
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