Overcoming genetic heterogeneity in industrial fermentations
Engineering the synthesis of massive amounts of therapeutics, enzymes or commodity chemicals can select for subpopulations of nonproducer cells, owing to metabolic burden and product toxicity. Deep DNA sequencing can be used to detect undesirable genetic heterogeneity in producer populations and dia...
Gespeichert in:
Veröffentlicht in: | Nature biotechnology 2019-08, Vol.37 (8), p.869-876 |
---|---|
Hauptverfasser: | , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 876 |
---|---|
container_issue | 8 |
container_start_page | 869 |
container_title | Nature biotechnology |
container_volume | 37 |
creator | Rugbjerg, Peter Sommer, Morten O. A. |
description | Engineering the synthesis of massive amounts of therapeutics, enzymes or commodity chemicals can select for subpopulations of nonproducer cells, owing to metabolic burden and product toxicity. Deep DNA sequencing can be used to detect undesirable genetic heterogeneity in producer populations and diagnose associated genetic error modes. Hotspots of genetic heterogeneity can pinpoint mechanisms that underlie load problems and product toxicity. Understanding genetic heterogeneity will inform metabolic engineering and synthetic biology strategies to minimize the emergence of nonproducer mutants in scaled-up fermentations and maximize product quality and yield.
Detection and mitigation of strain instability in industrial microbiology scale-up. |
doi_str_mv | 10.1038/s41587-019-0171-6 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2254507655</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2268063590</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-db9512beda267d343907941151bc2bf925a80e36c24e7cd61af0ae21e21617e93</originalsourceid><addsrcrecordid>eNp1kF1LwzAUhoMobk5_gDdS8Mabak7SpA14I8MvGOxGr0Pans6OfswkFfbvzexUEIQTknCe8yY8hJwDvQbKsxuXgMjSmIIKK4VYHpApiETGIJU8DGf61RVyQk6cW1NKZSLlMZlwYJkQik_J7fIDbdG3dbeKVtihr4voDT3afner_Taqu1Dl4LytTRNVaFvsvPF137lTclSZxuHZfp-R14f7l_lTvFg-Ps_vFnHBU-bjMlcCWI6lYTItecIVTVUCICAvWF4pJkxGkcuCJZgWpQRTUYMMQklIUfEZuRpzN7Z_H9B53dauwKYxHfaD04yJRNBUChHQyz_ouh9sF34XKJlRyYWigYKRKmzvnMVKb2zdGrvVQPVOrR7V6qBW79RqGWYu9slD3mL5M_HtMgBsBFxodSu0v0__n_oJWsyDEQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2268063590</pqid></control><display><type>article</type><title>Overcoming genetic heterogeneity in industrial fermentations</title><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Rugbjerg, Peter ; Sommer, Morten O. A.</creator><creatorcontrib>Rugbjerg, Peter ; Sommer, Morten O. A.</creatorcontrib><description>Engineering the synthesis of massive amounts of therapeutics, enzymes or commodity chemicals can select for subpopulations of nonproducer cells, owing to metabolic burden and product toxicity. Deep DNA sequencing can be used to detect undesirable genetic heterogeneity in producer populations and diagnose associated genetic error modes. Hotspots of genetic heterogeneity can pinpoint mechanisms that underlie load problems and product toxicity. Understanding genetic heterogeneity will inform metabolic engineering and synthetic biology strategies to minimize the emergence of nonproducer mutants in scaled-up fermentations and maximize product quality and yield.
Detection and mitigation of strain instability in industrial microbiology scale-up.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/s41587-019-0171-6</identifier><identifier>PMID: 31285593</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/181/457 ; 631/326/252 ; 631/61/318 ; 631/61/514/2254 ; Agriculture ; Bioinformatics ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; Error detection ; Heterogeneity ; Life Sciences ; Metabolic engineering ; Metabolism ; Nonproducer cells ; Organic chemistry ; Perspective ; Population genetics ; Subpopulations ; Toxicity</subject><ispartof>Nature biotechnology, 2019-08, Vol.37 (8), p.869-876</ispartof><rights>Springer Nature America, Inc. 2019</rights><rights>Copyright Nature Publishing Group Aug 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-db9512beda267d343907941151bc2bf925a80e36c24e7cd61af0ae21e21617e93</citedby><cites>FETCH-LOGICAL-c372t-db9512beda267d343907941151bc2bf925a80e36c24e7cd61af0ae21e21617e93</cites><orcidid>0000-0003-4005-5674 ; 0000-0003-2561-5063</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31285593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rugbjerg, Peter</creatorcontrib><creatorcontrib>Sommer, Morten O. A.</creatorcontrib><title>Overcoming genetic heterogeneity in industrial fermentations</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Engineering the synthesis of massive amounts of therapeutics, enzymes or commodity chemicals can select for subpopulations of nonproducer cells, owing to metabolic burden and product toxicity. Deep DNA sequencing can be used to detect undesirable genetic heterogeneity in producer populations and diagnose associated genetic error modes. Hotspots of genetic heterogeneity can pinpoint mechanisms that underlie load problems and product toxicity. Understanding genetic heterogeneity will inform metabolic engineering and synthetic biology strategies to minimize the emergence of nonproducer mutants in scaled-up fermentations and maximize product quality and yield.
Detection and mitigation of strain instability in industrial microbiology scale-up.</description><subject>631/181/457</subject><subject>631/326/252</subject><subject>631/61/318</subject><subject>631/61/514/2254</subject><subject>Agriculture</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Error detection</subject><subject>Heterogeneity</subject><subject>Life Sciences</subject><subject>Metabolic engineering</subject><subject>Metabolism</subject><subject>Nonproducer cells</subject><subject>Organic chemistry</subject><subject>Perspective</subject><subject>Population genetics</subject><subject>Subpopulations</subject><subject>Toxicity</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kF1LwzAUhoMobk5_gDdS8Mabak7SpA14I8MvGOxGr0Pans6OfswkFfbvzexUEIQTknCe8yY8hJwDvQbKsxuXgMjSmIIKK4VYHpApiETGIJU8DGf61RVyQk6cW1NKZSLlMZlwYJkQik_J7fIDbdG3dbeKVtihr4voDT3afner_Taqu1Dl4LytTRNVaFvsvPF137lTclSZxuHZfp-R14f7l_lTvFg-Ps_vFnHBU-bjMlcCWI6lYTItecIVTVUCICAvWF4pJkxGkcuCJZgWpQRTUYMMQklIUfEZuRpzN7Z_H9B53dauwKYxHfaD04yJRNBUChHQyz_ouh9sF34XKJlRyYWigYKRKmzvnMVKb2zdGrvVQPVOrR7V6qBW79RqGWYu9slD3mL5M_HtMgBsBFxodSu0v0__n_oJWsyDEQ</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Rugbjerg, Peter</creator><creator>Sommer, Morten O. A.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4005-5674</orcidid><orcidid>https://orcid.org/0000-0003-2561-5063</orcidid></search><sort><creationdate>20190801</creationdate><title>Overcoming genetic heterogeneity in industrial fermentations</title><author>Rugbjerg, Peter ; Sommer, Morten O. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-db9512beda267d343907941151bc2bf925a80e36c24e7cd61af0ae21e21617e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/181/457</topic><topic>631/326/252</topic><topic>631/61/318</topic><topic>631/61/514/2254</topic><topic>Agriculture</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA sequencing</topic><topic>Error detection</topic><topic>Heterogeneity</topic><topic>Life Sciences</topic><topic>Metabolic engineering</topic><topic>Metabolism</topic><topic>Nonproducer cells</topic><topic>Organic chemistry</topic><topic>Perspective</topic><topic>Population genetics</topic><topic>Subpopulations</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rugbjerg, Peter</creatorcontrib><creatorcontrib>Sommer, Morten O. A.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rugbjerg, Peter</au><au>Sommer, Morten O. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overcoming genetic heterogeneity in industrial fermentations</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>37</volume><issue>8</issue><spage>869</spage><epage>876</epage><pages>869-876</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><abstract>Engineering the synthesis of massive amounts of therapeutics, enzymes or commodity chemicals can select for subpopulations of nonproducer cells, owing to metabolic burden and product toxicity. Deep DNA sequencing can be used to detect undesirable genetic heterogeneity in producer populations and diagnose associated genetic error modes. Hotspots of genetic heterogeneity can pinpoint mechanisms that underlie load problems and product toxicity. Understanding genetic heterogeneity will inform metabolic engineering and synthetic biology strategies to minimize the emergence of nonproducer mutants in scaled-up fermentations and maximize product quality and yield.
Detection and mitigation of strain instability in industrial microbiology scale-up.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>31285593</pmid><doi>10.1038/s41587-019-0171-6</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4005-5674</orcidid><orcidid>https://orcid.org/0000-0003-2561-5063</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1087-0156 |
ispartof | Nature biotechnology, 2019-08, Vol.37 (8), p.869-876 |
issn | 1087-0156 1546-1696 |
language | eng |
recordid | cdi_proquest_miscellaneous_2254507655 |
source | Nature; Alma/SFX Local Collection |
subjects | 631/181/457 631/326/252 631/61/318 631/61/514/2254 Agriculture Bioinformatics Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Deoxyribonucleic acid DNA DNA sequencing Error detection Heterogeneity Life Sciences Metabolic engineering Metabolism Nonproducer cells Organic chemistry Perspective Population genetics Subpopulations Toxicity |
title | Overcoming genetic heterogeneity in industrial fermentations |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T21%3A34%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Overcoming%20genetic%20heterogeneity%20in%20industrial%20fermentations&rft.jtitle=Nature%20biotechnology&rft.au=Rugbjerg,%20Peter&rft.date=2019-08-01&rft.volume=37&rft.issue=8&rft.spage=869&rft.epage=876&rft.pages=869-876&rft.issn=1087-0156&rft.eissn=1546-1696&rft_id=info:doi/10.1038/s41587-019-0171-6&rft_dat=%3Cproquest_cross%3E2268063590%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2268063590&rft_id=info:pmid/31285593&rfr_iscdi=true |