Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis

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Biol.; citation_volume=18; citation_pages=601-607;citation_publication_date=2011; " /> <meta name="citation_reference" content="citation_author=J. Thirlway; citation_author=R. Lewis; citation_author=L. Nunns; citation_author=M. Al Nakeeb; citation_author=M. Styles; citation_author=A. W. Struck; citation_author=C. P. Smith; citation_author=J. Micklefield; citation_journal_title=Angew. Chem., Int. Ed.; citation_volume=51; citation_pages=7181-7184;citation_publication_date=2012; " /> <meta content=" Covering up to 2014 Nonribosomal peptides (NRPs) account for a large portion of drugs and drug leads currently available in the pharmaceutical industry. They are one of two main families of natural products biosynthesized on megaenzyme assembly-lines composed of multiple modules that are, in general, each comprised of three core domains and on occasion of accompanying auxiliary domains. The core adenylation (A) domains are known to delineate the identity of the specific chemical components to be incorporated into the growing NRPs. Previously believed to be inactive, A domains interrupted by auxiliary enzymes have recently been proven to be active and capable of performing two distinct chemical reactions. This highlight summarizes current knowledge on A domains and presents the various interrupted A domains found in a number of nonribosomal peptide synthetase (NRPS) assembly-lines, their predicted or proven dual functions, and their potential for manipulation and engineering for chemoenzymatic synthesis of new pharmaceutical agents with increased potency. 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Click to view all articles in this issue." title="Issue 5, 2015">Issue 5, 2015</a> </div> <nav aria-label="Article"> <ul class="article-nav__bar"> <li> <a href="/en/Content/ArticleLanding/2015/NP/C5NP90019K"> Previous <span class="v-mobile-hide--inline">Article</span> </a> </li> <li> <a href="/en/Content/ArticleLanding/2015/NP/C4NP00036F"> Next <span class="v-mobile-hide--inline">Article</span> </a> </li> </ul> </nav> <div class="list-control"> <div class="list__collection--image"> <div class="list__item"> <a href="/en/journals/journal/np" class="list__item-link"> <div class="list__image-col"> <img src="/en/Image/Get?imageInfo.ImageType=CoverIssue&imageInfo.ImageIdentifier.SerCode=NP&imageInfo.ImageIdentifier.IssueId=NP032005" id="imgLoader" alt="" class="list__item-img" height="88"> </div> <div class="list__text-col"> <div class="list__item-label"> <span class="page-head__context">From the journal:</span> <h3 class="h--heading3 no-heading">Natural Product Reports</h3> </div> </div> </a> </div> </div> </div> <br> </div> <article class="article-control"> <div class="article__title"> <h2 class="capsule__title fixpadv--m"> Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis </h2> <div class="fixpadv--m crossmark-button"> <button type="button" data-target="crossmark"><img width="150" height="32" src="https://crossmark-cdn.crossref.org/widget/v2.0/logos/CROSSMARK_Color_horizontal.svg" alt="Check for updates" /></button> </div> </div> <div class="article__authors"> <span class="article__author-link"> <a href="/en/results?searchtext=Author%3AKristin%20J.%20Labby">Kristin J. Labby</a>,<span><sup><i>a</i></sup></span>   </span> <span class="article__author-link"> <a href="/en/results?searchtext=Author%3AStoyan%20G.%20Watsula">Stoyan G. Watsula</a><span><sup><i>b</i></sup></span>  and  </span> <span class="article__author-link"> <a href="/en/results?searchtext=Author%3ASylvie%20Garneau-Tsodikova">Sylvie Garneau-Tsodikova</a>*<span><sup><i>c</i></sup></span>   </span> </div> <div class="drawer-control fixpadv--m"> <a href="#" role="button" id="btnAuthorAffiliations" aria-expanded="false" aria-controls="pnlAuthorAffiliations" class="drawer__handle"> <span class="drawer__icon"></span> Author affiliations </a> <div class="drawer__content" id="pnlAuthorAffiliations" aria-labelledby="btnAuthorAffiliations"> <div> <p class="article__author-affiliation"> <span> * </span> <span> Corresponding authors </span> </p> <p class="article__author-affiliation"> <span> <sup>a</sup> </span> <span> Beloit College, Department of Chemistry, 700 College Street, Beloit, WI 53511, USA </span> </p> <p class="article__author-affiliation"> <span> <sup>b</sup> </span> <span> University of Michigan, Department of Medicinal Chemistry in the College of Pharmacy, 210 Washtenaw Ave, Ann Arbor, MI 48109, USA </span> </p> <p class="article__author-affiliation"> <span> <sup>c</sup> </span> <span> University of Kentucky, Department of Pharmaceutical Sciences in the College of Pharmacy, BioPharm Complex, 789 South Limestone Street, Lexington, KY 40536-0596, USA <br /> <b>E-mail:</b> <a href="mailto:sylviegtsodikova@uky.edu" title="sylviegtsodikova@uky.edu">sylviegtsodikova@uky.edu</a> <br /> <b>Fax:</b> +1-859-257-7585 <br /> <b>Tel:</b> +1-859-218-1686 </span> </p> </div> </div> </div> <h3 class="h--heading3 article-abstract__heading">Abstract</h3> <div class="capsule__column-wrapper"> <div class="capsule__text"> <p xmlns="http://www.rsc.org/schema/rscart38">Covering up to 2014</p> <p xmlns="http://www.rsc.org/schema/rscart38">Nonribosomal peptides (NRPs) account for a large portion of drugs and drug leads currently available in the pharmaceutical industry. They are one of two main families of natural products biosynthesized on megaenzyme assembly-lines composed of multiple modules that are, in general, each comprised of three core domains and on occasion of accompanying auxiliary domains. The core adenylation (A) domains are known to delineate the identity of the specific chemical components to be incorporated into the growing NRPs. Previously believed to be inactive, A domains interrupted by auxiliary enzymes have recently been proven to be active and capable of performing two distinct chemical reactions. This highlight summarizes current knowledge on A domains and presents the various interrupted A domains found in a number of nonribosomal peptide synthetase (NRPS) assembly-lines, their predicted or proven dual functions, and their potential for manipulation and engineering for chemoenzymatic synthesis of new pharmaceutical agents with increased potency.</p> </div> <div class="capsule__article-image fixpadv--s"> <img src="/en/Image/Get?imageInfo.ImageType=GA&imageInfo.ImageIdentifier.ManuscriptID=C4NP00120F&imageInfo.ImageIdentifier.Year=2015" alt="Graphical abstract: Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis" /> </div> </div> <p></p> <div class="pnl pnl--border pnl--drop"> <div class="list-control"> <ul class="list__collection"> <li class="list__item"> This article is part of the themed collection: <a href="/en/journals/articlecollectionlanding?sercode=np&themeid=9ec966b9-0161-4261-8b8b-af5a1bfcfa50">Biosynthetic Assembly Lines</a> </li> </ul> </div> </div> <div id="pnlArticleAccess" class="article-access fixpadt--xxl" style="display: none; border: 0;"> <div class="article-access__inner" style="background-color: #F1F1F3;"> <div class="article-access__head fixpad--s"> You have access to this article </div> <div class="fixpad--xl"> <div id="pnlViewFullArticleButton" class="paywall__body text--centered"> <div id="pnlArticleLoading"> <span id="thtmlLoadingMessage"> <img src="https://www.rsc-cdn.org/pubs-core/2022.0.159/content/NewImages/Ajax-GA-Loader.gif" alt="" class="ver-m" /> Please wait while we load your content... </span> <span id="thtmlErrorMessage" style="display: none;"> Something went wrong. <a href="#" id="btnTryAgain">Try again?</a> </span> </div> </div> </div> </div> </div> <div id="pnlArticleContent" class="t-html"> <div id="pnlArticleContentLoaded"> </div> </div> </article> </section> </div> <div class="layout__panel layout__panel--secondary layout__panel--40 layout__panel--filled"> <section class="layout__content"> <input id="contentType" name="contentType" type="hidden" value="" /> <div class="tab-control"> <div class="tab__nav" role="tablist" aria-label="Article"> <div class="tab__item" role="none"> <a href="#pnlAbstract" class="tab__btn selected" role="tab" id="btnAbstract" aria-selected="true" aria-controls="pnlAbstract">About</a> </div> <div class="tab__item" role="none"> <a href="#pnlCitation" class="tab__btn" role="tab" id="btnCitation" aria-selected="false" aria-controls="pnlCitation">Cited by</a> </div> <div class="tab__item" role="none"> <a href="#pnlRelatedContent" class="tab__btn" role="tab" id="btnRelatedContent" aria-selected="false" aria-controls="pnlRelatedContent">Related</a> </div> </div> <div class="tab__panel open" role="tabpanel" id="pnlAbstract" aria-hidden="false" aria-labelledby="btnAbstract" data-loaded="true"> <div class="fixpadv--m"> <div id="divAbout"> <div id="DownloadOption" class="autopad--h fixpadv--l" style="min-height: 150px;"> <div class="text--centered"> <a href="#" class="btn btn--cta btn--disabled btn--block btn--stack btn-icon btn-icon--loading"> Download options <span class="btn-info">Please wait...</span> </a> </div> </div> <div class="autopad--h"> <h2 class="h--heading3">Article information</h2> <dl class="definition-list"> <div class="c doi-link"> <dt class="sr-only">DOI</dt> <dd class="c__24"><a class="text--small" title="Link to landing page via DOI" href="https://doi.org/10.1039/C4NP00120F">https://doi.org/10.1039/C4NP00120F</a></dd> </div> <div class="c fixpadt--l line-separator"> <dt class="c__10"><strong>Article type</strong></dt> <dd class="c__14">Highlight</dd> </div> <div class="c fixpadt--l"> <dt class="c__10">Submitted</dt> <dd class="c__14">15 Sep 2014</dd> </div> <div class="c fixpadt--l"> <dt class="c__10">First published</dt> <dd class="c__14">27 Jan 2015</dd> </div> </dl> <div class="c fixpadt--l line-separator"> <div class="c__10"> <h3 class="definition-label"> <label for="ResultAbstractFormat"><span class="sr-only">Download</span> Citation</label> </h3> </div> <div class="c__14"> <i><strong>Nat. 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Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis - Natural Product Reports (RSC Publishing)