Semi-rational mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity
The biosynthesis of the valuable antibiotic enduracidin by Streptomyces fungicidicus TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Co...
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| Veröffentlicht in: | Applied microbiology and biotechnology 2020-04, Vol.104 (8), p.3459-3471 |
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| creator | Zhang, Jing He, Zilong Xu, JinTian Song, Shuting Zhu, Qianhui Wu, Guoguo Guan, Ying Wu, Xiaonong Yue, Rong Wang, Yue Yu, Tao Hu, Songnian Lu, Fuping Zhang, Huitu |
| description | The biosynthesis of the valuable antibiotic enduracidin by
Streptomyces fungicidicus
TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Comparative RNA-seq analysis indicated that the expression level of the
endC
gene during the enduracidin production phase was evidently lower than that of the other relevant genes to enduracidin biosynthesis. This result was further confirmed by quantitative RT-PCR, and the giant non-ribosomal peptide synthase (NRPS) encoded by
endC
was predicated to be the rate-limiting enzyme in enduracidin biosynthesis. To increase the expression of
endC
during the enduracidin production phase, a reporter-based selection system was developed by genetically replacing the initial part of the
endC
gene with a thiostrepton resistance gene (
tsr
), which will then act as a selectable marker to report the expression level of the rate-limiting gene
endC
, thereby facilitating the selection of enduracidin-overproducing mutants following random mutagenesis. After one round of mutagenesis, thiostrepton resistance selection, and restoration of the
endC
gene, three mutant strains with improved
endC
expression levels were obtained. Their highest enduracidin titers reached 9780.54, 9272.46, and 8849.06 U/mL, respectively representing 2.31-, 2.19-, and 2.09-fold of the initial industrial strain TXX3120. Our research provides a useful strategy for the rational breeding of industrial strains that synthesize complex natural products.
Key Points
•
Dynamic analysis of the expression profiles of enduracidin gene cluster revealed the rate-limiting step for enduracidin biosynthesis.
•
Construction of a transcriptionally linked selection marker system for directional breeding of an industrially used enduracidin-producing strain.
•
An efficient method for selecting mutants with improved end-product titers, which overcomes uncertainty of random selection and the blindness. |
| doi_str_mv | 10.1007/s00253-020-10488-0 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2381960349</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A618388665</galeid><sourcerecordid>A618388665</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-31220faf2bc41f67c990494f9fe3ed9bc16a0edccec8c837a8f8c874129c923f3</originalsourceid><addsrcrecordid>eNp9kV9rVDEQxYModq1-AR8k4JMPqZPk_kkeS9FaKAiuPods7uSSsjd3m-SW7rc37VbLgkgeBmZ-Z8KZQ8h7DmccoP-cAUQrGQhgHBqlGLwgK95IwaDjzUuyAt63rG-1OiFvcr4B4EJ13WtyIgXoVnV8RW7XOAWWbAlztFs6LcWOGDGHTGdPbaQhDksuKdThuiTclXnaO8zUL3EMLgzBLZlWwIZI_ZxomHZpvsOBYhUm-0BEWlvD4kq4C2X_lrzydpvx3VM9Jb--fvl58Y1df7-8uji_Zq7lsjDJhQBvvdi4hvuud1pDoxuvPUoc9MbxzgIOzqFTTsneKl9r33ChnRbSy1Py8bC3fn67YC7mZl5SNZmNkIrrDmSjn6nRbtGE6OdqxU0hO3PecSVVPVhbqbN_UPUN9XpujuhD7R8JPh0JKlPwvox2ydlcrX8cs-LAujTnnNCbXQqTTXvDwTwEbQ5Bmxq0eQzaQBV9eHK3bCYc_kr-JFsBeQByHcUR07P9_6z9DUqMtDY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2381960349</pqid></control><display><type>article</type><title>Semi-rational mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, Jing ; He, Zilong ; Xu, JinTian ; Song, Shuting ; Zhu, Qianhui ; Wu, Guoguo ; Guan, Ying ; Wu, Xiaonong ; Yue, Rong ; Wang, Yue ; Yu, Tao ; Hu, Songnian ; Lu, Fuping ; Zhang, Huitu</creator><creatorcontrib>Zhang, Jing ; He, Zilong ; Xu, JinTian ; Song, Shuting ; Zhu, Qianhui ; Wu, Guoguo ; Guan, Ying ; Wu, Xiaonong ; Yue, Rong ; Wang, Yue ; Yu, Tao ; Hu, Songnian ; Lu, Fuping ; Zhang, Huitu</creatorcontrib><description>The biosynthesis of the valuable antibiotic enduracidin by
Streptomyces fungicidicus
TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Comparative RNA-seq analysis indicated that the expression level of the
endC
gene during the enduracidin production phase was evidently lower than that of the other relevant genes to enduracidin biosynthesis. This result was further confirmed by quantitative RT-PCR, and the giant non-ribosomal peptide synthase (NRPS) encoded by
endC
was predicated to be the rate-limiting enzyme in enduracidin biosynthesis. To increase the expression of
endC
during the enduracidin production phase, a reporter-based selection system was developed by genetically replacing the initial part of the
endC
gene with a thiostrepton resistance gene (
tsr
), which will then act as a selectable marker to report the expression level of the rate-limiting gene
endC
, thereby facilitating the selection of enduracidin-overproducing mutants following random mutagenesis. After one round of mutagenesis, thiostrepton resistance selection, and restoration of the
endC
gene, three mutant strains with improved
endC
expression levels were obtained. Their highest enduracidin titers reached 9780.54, 9272.46, and 8849.06 U/mL, respectively representing 2.31-, 2.19-, and 2.09-fold of the initial industrial strain TXX3120. Our research provides a useful strategy for the rational breeding of industrial strains that synthesize complex natural products.
Key Points
•
Dynamic analysis of the expression profiles of enduracidin gene cluster revealed the rate-limiting step for enduracidin biosynthesis.
•
Construction of a transcriptionally linked selection marker system for directional breeding of an industrially used enduracidin-producing strain.
•
An efficient method for selecting mutants with improved end-product titers, which overcomes uncertainty of random selection and the blindness.</description><identifier>ISSN: 0175-7598</identifier><identifier>EISSN: 1432-0614</identifier><identifier>DOI: 10.1007/s00253-020-10488-0</identifier><identifier>PMID: 32095861</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Analysis ; Anti-Bacterial Agents - biosynthesis ; Antibiotics ; Applied Genetics and Molecular Biotechnology ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Biomarkers ; Biomedical and Life Sciences ; Biosynthesis ; Biosynthetic Pathways - genetics ; Biotechnology ; Blindness ; Breeding ; Constraining ; Enduracidin ; Enzymes ; Fatigue limit ; Fermentation ; Gene expression ; Gene sequencing ; Industrial strains ; Life Sciences ; Methicillin ; Microbial Genetics and Genomics ; Microbiology ; Multigene Family ; Mutagenesis ; Mutants ; Mycelia ; Natural products ; Niacin - biosynthesis ; Non-ribosomal peptide synthase ; Peptide synthase ; Peptide Synthases - genetics ; Peptide Synthases - metabolism ; Polymerase chain reaction ; Random mutagenesis ; Restoration ; Ribonucleic acid ; RNA ; RNA sequencing ; RNA-Seq ; Streptomyces ; Streptomyces - enzymology ; Streptomyces - genetics ; Thiostrepton ; Thiostrepton - pharmacology ; Transcription</subject><ispartof>Applied microbiology and biotechnology, 2020-04, Vol.104 (8), p.3459-3471</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Applied Microbiology and Biotechnology is a copyright of Springer, (2020). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-31220faf2bc41f67c990494f9fe3ed9bc16a0edccec8c837a8f8c874129c923f3</citedby><cites>FETCH-LOGICAL-c513t-31220faf2bc41f67c990494f9fe3ed9bc16a0edccec8c837a8f8c874129c923f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00253-020-10488-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00253-020-10488-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32095861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>He, Zilong</creatorcontrib><creatorcontrib>Xu, JinTian</creatorcontrib><creatorcontrib>Song, Shuting</creatorcontrib><creatorcontrib>Zhu, Qianhui</creatorcontrib><creatorcontrib>Wu, Guoguo</creatorcontrib><creatorcontrib>Guan, Ying</creatorcontrib><creatorcontrib>Wu, Xiaonong</creatorcontrib><creatorcontrib>Yue, Rong</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Hu, Songnian</creatorcontrib><creatorcontrib>Lu, Fuping</creatorcontrib><creatorcontrib>Zhang, Huitu</creatorcontrib><title>Semi-rational mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity</title><title>Applied microbiology and biotechnology</title><addtitle>Appl Microbiol Biotechnol</addtitle><addtitle>Appl Microbiol Biotechnol</addtitle><description>The biosynthesis of the valuable antibiotic enduracidin by
Streptomyces fungicidicus
TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Comparative RNA-seq analysis indicated that the expression level of the
endC
gene during the enduracidin production phase was evidently lower than that of the other relevant genes to enduracidin biosynthesis. This result was further confirmed by quantitative RT-PCR, and the giant non-ribosomal peptide synthase (NRPS) encoded by
endC
was predicated to be the rate-limiting enzyme in enduracidin biosynthesis. To increase the expression of
endC
during the enduracidin production phase, a reporter-based selection system was developed by genetically replacing the initial part of the
endC
gene with a thiostrepton resistance gene (
tsr
), which will then act as a selectable marker to report the expression level of the rate-limiting gene
endC
, thereby facilitating the selection of enduracidin-overproducing mutants following random mutagenesis. After one round of mutagenesis, thiostrepton resistance selection, and restoration of the
endC
gene, three mutant strains with improved
endC
expression levels were obtained. Their highest enduracidin titers reached 9780.54, 9272.46, and 8849.06 U/mL, respectively representing 2.31-, 2.19-, and 2.09-fold of the initial industrial strain TXX3120. Our research provides a useful strategy for the rational breeding of industrial strains that synthesize complex natural products.
Key Points
•
Dynamic analysis of the expression profiles of enduracidin gene cluster revealed the rate-limiting step for enduracidin biosynthesis.
•
Construction of a transcriptionally linked selection marker system for directional breeding of an industrially used enduracidin-producing strain.
•
An efficient method for selecting mutants with improved end-product titers, which overcomes uncertainty of random selection and the blindness.</description><subject>Analysis</subject><subject>Anti-Bacterial Agents - biosynthesis</subject><subject>Antibiotics</subject><subject>Applied Genetics and Molecular Biotechnology</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>Biosynthetic Pathways - genetics</subject><subject>Biotechnology</subject><subject>Blindness</subject><subject>Breeding</subject><subject>Constraining</subject><subject>Enduracidin</subject><subject>Enzymes</subject><subject>Fatigue limit</subject><subject>Fermentation</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Industrial strains</subject><subject>Life Sciences</subject><subject>Methicillin</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>Multigene Family</subject><subject>Mutagenesis</subject><subject>Mutants</subject><subject>Mycelia</subject><subject>Natural products</subject><subject>Niacin - biosynthesis</subject><subject>Non-ribosomal peptide synthase</subject><subject>Peptide synthase</subject><subject>Peptide Synthases - genetics</subject><subject>Peptide Synthases - metabolism</subject><subject>Polymerase chain reaction</subject><subject>Random mutagenesis</subject><subject>Restoration</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA-Seq</subject><subject>Streptomyces</subject><subject>Streptomyces - enzymology</subject><subject>Streptomyces - genetics</subject><subject>Thiostrepton</subject><subject>Thiostrepton - pharmacology</subject><subject>Transcription</subject><issn>0175-7598</issn><issn>1432-0614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kV9rVDEQxYModq1-AR8k4JMPqZPk_kkeS9FaKAiuPods7uSSsjd3m-SW7rc37VbLgkgeBmZ-Z8KZQ8h7DmccoP-cAUQrGQhgHBqlGLwgK95IwaDjzUuyAt63rG-1OiFvcr4B4EJ13WtyIgXoVnV8RW7XOAWWbAlztFs6LcWOGDGHTGdPbaQhDksuKdThuiTclXnaO8zUL3EMLgzBLZlWwIZI_ZxomHZpvsOBYhUm-0BEWlvD4kq4C2X_lrzydpvx3VM9Jb--fvl58Y1df7-8uji_Zq7lsjDJhQBvvdi4hvuud1pDoxuvPUoc9MbxzgIOzqFTTsneKl9r33ChnRbSy1Py8bC3fn67YC7mZl5SNZmNkIrrDmSjn6nRbtGE6OdqxU0hO3PecSVVPVhbqbN_UPUN9XpujuhD7R8JPh0JKlPwvox2ydlcrX8cs-LAujTnnNCbXQqTTXvDwTwEbQ5Bmxq0eQzaQBV9eHK3bCYc_kr-JFsBeQByHcUR07P9_6z9DUqMtDY</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Zhang, Jing</creator><creator>He, Zilong</creator><creator>Xu, JinTian</creator><creator>Song, Shuting</creator><creator>Zhu, Qianhui</creator><creator>Wu, Guoguo</creator><creator>Guan, Ying</creator><creator>Wu, Xiaonong</creator><creator>Yue, Rong</creator><creator>Wang, Yue</creator><creator>Yu, Tao</creator><creator>Hu, Songnian</creator><creator>Lu, Fuping</creator><creator>Zhang, Huitu</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature 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mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity</title><author>Zhang, Jing ; He, Zilong ; Xu, JinTian ; Song, Shuting ; Zhu, Qianhui ; Wu, Guoguo ; Guan, Ying ; Wu, Xiaonong ; Yue, Rong ; Wang, Yue ; Yu, Tao ; Hu, Songnian ; Lu, Fuping ; Zhang, Huitu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-31220faf2bc41f67c990494f9fe3ed9bc16a0edccec8c837a8f8c874129c923f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Anti-Bacterial Agents - biosynthesis</topic><topic>Antibiotics</topic><topic>Applied Genetics and Molecular Biotechnology</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>Biosynthetic Pathways - genetics</topic><topic>Biotechnology</topic><topic>Blindness</topic><topic>Breeding</topic><topic>Constraining</topic><topic>Enduracidin</topic><topic>Enzymes</topic><topic>Fatigue limit</topic><topic>Fermentation</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Industrial strains</topic><topic>Life Sciences</topic><topic>Methicillin</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Multigene Family</topic><topic>Mutagenesis</topic><topic>Mutants</topic><topic>Mycelia</topic><topic>Natural products</topic><topic>Niacin - biosynthesis</topic><topic>Non-ribosomal peptide synthase</topic><topic>Peptide synthase</topic><topic>Peptide Synthases - genetics</topic><topic>Peptide Synthases - metabolism</topic><topic>Polymerase chain reaction</topic><topic>Random mutagenesis</topic><topic>Restoration</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>RNA-Seq</topic><topic>Streptomyces</topic><topic>Streptomyces - enzymology</topic><topic>Streptomyces - genetics</topic><topic>Thiostrepton</topic><topic>Thiostrepton - pharmacology</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>He, Zilong</creatorcontrib><creatorcontrib>Xu, JinTian</creatorcontrib><creatorcontrib>Song, Shuting</creatorcontrib><creatorcontrib>Zhu, Qianhui</creatorcontrib><creatorcontrib>Wu, Guoguo</creatorcontrib><creatorcontrib>Guan, Ying</creatorcontrib><creatorcontrib>Wu, Xiaonong</creatorcontrib><creatorcontrib>Yue, Rong</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Hu, Songnian</creatorcontrib><creatorcontrib>Lu, Fuping</creatorcontrib><creatorcontrib>Zhang, 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mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity</atitle><jtitle>Applied microbiology and biotechnology</jtitle><stitle>Appl Microbiol Biotechnol</stitle><addtitle>Appl Microbiol Biotechnol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>104</volume><issue>8</issue><spage>3459</spage><epage>3471</epage><pages>3459-3471</pages><issn>0175-7598</issn><eissn>1432-0614</eissn><abstract>The biosynthesis of the valuable antibiotic enduracidin by
Streptomyces fungicidicus
TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Comparative RNA-seq analysis indicated that the expression level of the
endC
gene during the enduracidin production phase was evidently lower than that of the other relevant genes to enduracidin biosynthesis. This result was further confirmed by quantitative RT-PCR, and the giant non-ribosomal peptide synthase (NRPS) encoded by
endC
was predicated to be the rate-limiting enzyme in enduracidin biosynthesis. To increase the expression of
endC
during the enduracidin production phase, a reporter-based selection system was developed by genetically replacing the initial part of the
endC
gene with a thiostrepton resistance gene (
tsr
), which will then act as a selectable marker to report the expression level of the rate-limiting gene
endC
, thereby facilitating the selection of enduracidin-overproducing mutants following random mutagenesis. After one round of mutagenesis, thiostrepton resistance selection, and restoration of the
endC
gene, three mutant strains with improved
endC
expression levels were obtained. Their highest enduracidin titers reached 9780.54, 9272.46, and 8849.06 U/mL, respectively representing 2.31-, 2.19-, and 2.09-fold of the initial industrial strain TXX3120. Our research provides a useful strategy for the rational breeding of industrial strains that synthesize complex natural products.
Key Points
•
Dynamic analysis of the expression profiles of enduracidin gene cluster revealed the rate-limiting step for enduracidin biosynthesis.
•
Construction of a transcriptionally linked selection marker system for directional breeding of an industrially used enduracidin-producing strain.
•
An efficient method for selecting mutants with improved end-product titers, which overcomes uncertainty of random selection and the blindness.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32095861</pmid><doi>10.1007/s00253-020-10488-0</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0175-7598 |
| ispartof | Applied microbiology and biotechnology, 2020-04, Vol.104 (8), p.3459-3471 |
| issn | 0175-7598 1432-0614 |
| language | eng |
| recordid | cdi_proquest_journals_2381960349 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Anti-Bacterial Agents - biosynthesis Antibiotics Applied Genetics and Molecular Biotechnology Bacterial Proteins - genetics Bacterial Proteins - metabolism Biomarkers Biomedical and Life Sciences Biosynthesis Biosynthetic Pathways - genetics Biotechnology Blindness Breeding Constraining Enduracidin Enzymes Fatigue limit Fermentation Gene expression Gene sequencing Industrial strains Life Sciences Methicillin Microbial Genetics and Genomics Microbiology Multigene Family Mutagenesis Mutants Mycelia Natural products Niacin - biosynthesis Non-ribosomal peptide synthase Peptide synthase Peptide Synthases - genetics Peptide Synthases - metabolism Polymerase chain reaction Random mutagenesis Restoration Ribonucleic acid RNA RNA sequencing RNA-Seq Streptomyces Streptomyces - enzymology Streptomyces - genetics Thiostrepton Thiostrepton - pharmacology Transcription |
| title | Semi-rational mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T13%3A10%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Semi-rational%20mutagenesis%20of%20an%20industrial%20Streptomyces%20fungicidicus%20strain%20for%20improved%20enduracidin%20productivity&rft.jtitle=Applied%20microbiology%20and%20biotechnology&rft.au=Zhang,%20Jing&rft.date=2020-04-01&rft.volume=104&rft.issue=8&rft.spage=3459&rft.epage=3471&rft.pages=3459-3471&rft.issn=0175-7598&rft.eissn=1432-0614&rft_id=info:doi/10.1007/s00253-020-10488-0&rft_dat=%3Cgale_proqu%3EA618388665%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2381960349&rft_id=info:pmid/32095861&rft_galeid=A618388665&rfr_iscdi=true |