Macrophage-targeting oligopeptides from Mortierella alpina

The realm of natural products of early diverging fungi such as Mortierella species is largely unexplored. Herein, the nonribosomal peptide synthetase (NRPS) MalA catalysing the biosynthesis of the surface-active biosurfactants, malpinins, has been identified and biochemically characterised. The inve...

Full description

Saved in:
Bibliographic Details
Published in:Chemical science (Cambridge) 2022-08, Vol.13 (31), p.9091-9101
Main Authors: Wurlitzer, Jacob M., Stanišić, Aleksa, Ziethe, Sebastian, Jordan, Paul M., Günther, Kerstin, Werz, Oliver, Kries, Hajo, Gressler, Markus
Format: Article
Language:English
Subjects:
Amino acids
Biosynthesis
Cell membranes
Chemistry
Congeners
Fluorescence
Fungi
Modules
Natural products
Peptides
Substrates
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433
cites cdi_FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433
container_end_page 9101
container_issue 31
container_start_page 9091
container_title Chemical science (Cambridge)
container_volume 13
creator Wurlitzer, Jacob M.
Stanišić, Aleksa
Ziethe, Sebastian
Jordan, Paul M.
Günther, Kerstin
Werz, Oliver
Kries, Hajo
Gressler, Markus
description The realm of natural products of early diverging fungi such as Mortierella species is largely unexplored. Herein, the nonribosomal peptide synthetase (NRPS) MalA catalysing the biosynthesis of the surface-active biosurfactants, malpinins, has been identified and biochemically characterised. The investigation of the substrate specificity of respective adenylation (A) domains indicated a substrate-tolerant enzyme with an unusual, inactive C-terminal NRPS module. Specificity-based precursor-directed biosynthesis yielded 20 new congeners produced by a single enzyme. Moreover, MalA incorporates artificial, click-functionalised amino acids which allowed postbiosynthetic coupling to a fluorophore. The fluorescent malpinin conjugate penetrates mammalian cell membranes via an phagocytosis-mediated mechanism, suggesting Mortierella oligopeptides as carrier peptides for directed cell targeting. The current study demonstrates substrate-specificity testing as a powerful tool to identify flexible NRPS modules and highlights basal fungi as reservoir for chemically tractable compounds in pharmaceutical applications.
doi_str_mv 10.1039/d2sc00860b
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9365243</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2713309690</sourcerecordid><originalsourceid>FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433</originalsourceid><addsrcrecordid>eNpdkU1Lw0AQhhdRbKm9-AsCXkSIzn5km_UgaP2EFg_qedkkm3RLko27ieC_d1tLQecyA_Pw8r4zCJ1iuMRAxVVBfA6QcsgO0JgAwzFPqDjczwRGaOr9GkJRihMyO0YjykFggtkYXS9V7my3UpWOe-Uq3Zu2imxtKtvprjeF9lHpbBMtreuNdrquVaTqzrTqBB2VqvZ6uusT9PH48D5_jhevTy_z20WcU0z7mCuVzTAtOMeCzVjCec61wCUhheaMZIJrwCkpVVESXuSMs7RgCsoEgLGUUTpBN7-63ZA1ush12ztVy86ZRrlvaZWRfzetWcnKfklBQ_ytwPlOwNnPQfteNsbnmySttoOXJNijILiAgJ79Q9d2cG2IF6hgCFOcpoG6-KXC6bx3utybwSA3X5H35G2-_cod_QHhZXzg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2700413188</pqid></control><display><type>article</type><title>Macrophage-targeting oligopeptides from Mortierella alpina</title><source>PubMed Central</source><creator>Wurlitzer, Jacob M. ; Stanišić, Aleksa ; Ziethe, Sebastian ; Jordan, Paul M. ; Günther, Kerstin ; Werz, Oliver ; Kries, Hajo ; Gressler, Markus</creator><creatorcontrib>Wurlitzer, Jacob M. ; Stanišić, Aleksa ; Ziethe, Sebastian ; Jordan, Paul M. ; Günther, Kerstin ; Werz, Oliver ; Kries, Hajo ; Gressler, Markus</creatorcontrib><description>The realm of natural products of early diverging fungi such as Mortierella species is largely unexplored. Herein, the nonribosomal peptide synthetase (NRPS) MalA catalysing the biosynthesis of the surface-active biosurfactants, malpinins, has been identified and biochemically characterised. The investigation of the substrate specificity of respective adenylation (A) domains indicated a substrate-tolerant enzyme with an unusual, inactive C-terminal NRPS module. Specificity-based precursor-directed biosynthesis yielded 20 new congeners produced by a single enzyme. Moreover, MalA incorporates artificial, click-functionalised amino acids which allowed postbiosynthetic coupling to a fluorophore. The fluorescent malpinin conjugate penetrates mammalian cell membranes via an phagocytosis-mediated mechanism, suggesting Mortierella oligopeptides as carrier peptides for directed cell targeting. The current study demonstrates substrate-specificity testing as a powerful tool to identify flexible NRPS modules and highlights basal fungi as reservoir for chemically tractable compounds in pharmaceutical applications.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/d2sc00860b</identifier><identifier>PMID: 36091214</identifier><language>eng</language><publisher>Cambridge: Royal Society of Chemistry</publisher><subject>Amino acids ; Biosynthesis ; Cell membranes ; Chemistry ; Congeners ; Fluorescence ; Fungi ; Modules ; Natural products ; Peptides ; Substrates</subject><ispartof>Chemical science (Cambridge), 2022-08, Vol.13 (31), p.9091-9101</ispartof><rights>Copyright Royal Society of Chemistry 2022</rights><rights>This journal is © The Royal Society of Chemistry 2022 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433</citedby><cites>FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433</cites><orcidid>0000-0002-4919-2811 ; 0000-0002-5064-4379 ; 0000-0001-5669-7618 ; 0000-0001-8230-5972 ; 0000-0002-8364-4236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365243/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365243/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids></links><search><creatorcontrib>Wurlitzer, Jacob M.</creatorcontrib><creatorcontrib>Stanišić, Aleksa</creatorcontrib><creatorcontrib>Ziethe, Sebastian</creatorcontrib><creatorcontrib>Jordan, Paul M.</creatorcontrib><creatorcontrib>Günther, Kerstin</creatorcontrib><creatorcontrib>Werz, Oliver</creatorcontrib><creatorcontrib>Kries, Hajo</creatorcontrib><creatorcontrib>Gressler, Markus</creatorcontrib><title>Macrophage-targeting oligopeptides from Mortierella alpina</title><title>Chemical science (Cambridge)</title><description>The realm of natural products of early diverging fungi such as Mortierella species is largely unexplored. Herein, the nonribosomal peptide synthetase (NRPS) MalA catalysing the biosynthesis of the surface-active biosurfactants, malpinins, has been identified and biochemically characterised. The investigation of the substrate specificity of respective adenylation (A) domains indicated a substrate-tolerant enzyme with an unusual, inactive C-terminal NRPS module. Specificity-based precursor-directed biosynthesis yielded 20 new congeners produced by a single enzyme. Moreover, MalA incorporates artificial, click-functionalised amino acids which allowed postbiosynthetic coupling to a fluorophore. The fluorescent malpinin conjugate penetrates mammalian cell membranes via an phagocytosis-mediated mechanism, suggesting Mortierella oligopeptides as carrier peptides for directed cell targeting. The current study demonstrates substrate-specificity testing as a powerful tool to identify flexible NRPS modules and highlights basal fungi as reservoir for chemically tractable compounds in pharmaceutical applications.</description><subject>Amino acids</subject><subject>Biosynthesis</subject><subject>Cell membranes</subject><subject>Chemistry</subject><subject>Congeners</subject><subject>Fluorescence</subject><subject>Fungi</subject><subject>Modules</subject><subject>Natural products</subject><subject>Peptides</subject><subject>Substrates</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpdkU1Lw0AQhhdRbKm9-AsCXkSIzn5km_UgaP2EFg_qedkkm3RLko27ieC_d1tLQecyA_Pw8r4zCJ1iuMRAxVVBfA6QcsgO0JgAwzFPqDjczwRGaOr9GkJRihMyO0YjykFggtkYXS9V7my3UpWOe-Uq3Zu2imxtKtvprjeF9lHpbBMtreuNdrquVaTqzrTqBB2VqvZ6uusT9PH48D5_jhevTy_z20WcU0z7mCuVzTAtOMeCzVjCec61wCUhheaMZIJrwCkpVVESXuSMs7RgCsoEgLGUUTpBN7-63ZA1ush12ztVy86ZRrlvaZWRfzetWcnKfklBQ_ytwPlOwNnPQfteNsbnmySttoOXJNijILiAgJ79Q9d2cG2IF6hgCFOcpoG6-KXC6bx3utybwSA3X5H35G2-_cod_QHhZXzg</recordid><startdate>20220810</startdate><enddate>20220810</enddate><creator>Wurlitzer, Jacob M.</creator><creator>Stanišić, Aleksa</creator><creator>Ziethe, Sebastian</creator><creator>Jordan, Paul M.</creator><creator>Günther, Kerstin</creator><creator>Werz, Oliver</creator><creator>Kries, Hajo</creator><creator>Gressler, Markus</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4919-2811</orcidid><orcidid>https://orcid.org/0000-0002-5064-4379</orcidid><orcidid>https://orcid.org/0000-0001-5669-7618</orcidid><orcidid>https://orcid.org/0000-0001-8230-5972</orcidid><orcidid>https://orcid.org/0000-0002-8364-4236</orcidid></search><sort><creationdate>20220810</creationdate><title>Macrophage-targeting oligopeptides from Mortierella alpina</title><author>Wurlitzer, Jacob M. ; Stanišić, Aleksa ; Ziethe, Sebastian ; Jordan, Paul M. ; Günther, Kerstin ; Werz, Oliver ; Kries, Hajo ; Gressler, Markus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amino acids</topic><topic>Biosynthesis</topic><topic>Cell membranes</topic><topic>Chemistry</topic><topic>Congeners</topic><topic>Fluorescence</topic><topic>Fungi</topic><topic>Modules</topic><topic>Natural products</topic><topic>Peptides</topic><topic>Substrates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wurlitzer, Jacob M.</creatorcontrib><creatorcontrib>Stanišić, Aleksa</creatorcontrib><creatorcontrib>Ziethe, Sebastian</creatorcontrib><creatorcontrib>Jordan, Paul M.</creatorcontrib><creatorcontrib>Günther, Kerstin</creatorcontrib><creatorcontrib>Werz, Oliver</creatorcontrib><creatorcontrib>Kries, Hajo</creatorcontrib><creatorcontrib>Gressler, Markus</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wurlitzer, Jacob M.</au><au>Stanišić, Aleksa</au><au>Ziethe, Sebastian</au><au>Jordan, Paul M.</au><au>Günther, Kerstin</au><au>Werz, Oliver</au><au>Kries, Hajo</au><au>Gressler, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Macrophage-targeting oligopeptides from Mortierella alpina</atitle><jtitle>Chemical science (Cambridge)</jtitle><date>2022-08-10</date><risdate>2022</risdate><volume>13</volume><issue>31</issue><spage>9091</spage><epage>9101</epage><pages>9091-9101</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>The realm of natural products of early diverging fungi such as Mortierella species is largely unexplored. Herein, the nonribosomal peptide synthetase (NRPS) MalA catalysing the biosynthesis of the surface-active biosurfactants, malpinins, has been identified and biochemically characterised. The investigation of the substrate specificity of respective adenylation (A) domains indicated a substrate-tolerant enzyme with an unusual, inactive C-terminal NRPS module. Specificity-based precursor-directed biosynthesis yielded 20 new congeners produced by a single enzyme. Moreover, MalA incorporates artificial, click-functionalised amino acids which allowed postbiosynthetic coupling to a fluorophore. The fluorescent malpinin conjugate penetrates mammalian cell membranes via an phagocytosis-mediated mechanism, suggesting Mortierella oligopeptides as carrier peptides for directed cell targeting. The current study demonstrates substrate-specificity testing as a powerful tool to identify flexible NRPS modules and highlights basal fungi as reservoir for chemically tractable compounds in pharmaceutical applications.</abstract><cop>Cambridge</cop><pub>Royal Society of Chemistry</pub><pmid>36091214</pmid><doi>10.1039/d2sc00860b</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4919-2811</orcidid><orcidid>https://orcid.org/0000-0002-5064-4379</orcidid><orcidid>https://orcid.org/0000-0001-5669-7618</orcidid><orcidid>https://orcid.org/0000-0001-8230-5972</orcidid><orcidid>https://orcid.org/0000-0002-8364-4236</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2041-6520
ispartof Chemical science (Cambridge), 2022-08, Vol.13 (31), p.9091-9101
issn 2041-6520
2041-6539
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9365243
source PubMed Central
subjects Amino acids
Biosynthesis
Cell membranes
Chemistry
Congeners
Fluorescence
Fungi
Modules
Natural products
Peptides
Substrates
title Macrophage-targeting oligopeptides from Mortierella alpina
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T13%3A45%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Macrophage-targeting%20oligopeptides%20from%20Mortierella%20alpina&rft.jtitle=Chemical%20science%20(Cambridge)&rft.au=Wurlitzer,%20Jacob%20M.&rft.date=2022-08-10&rft.volume=13&rft.issue=31&rft.spage=9091&rft.epage=9101&rft.pages=9091-9101&rft.issn=2041-6520&rft.eissn=2041-6539&rft_id=info:doi/10.1039/d2sc00860b&rft_dat=%3Cproquest_pubme%3E2713309690%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c313t-6aab713d6619474566c6e91f22de642b96e0182fadf26dc4648d4a0f500448433%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2700413188&rft_id=info:pmid/36091214&rfr_iscdi=true