Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007
Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-gen...
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creator | Liu, Ran Fang, Fang An, Ziheng Huang, Renqiong Wang, Yong Sun, Xiao Fu, Shuai Fu, Aisi Deng, Zixin Liu, Tiangang |
description | Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of
Actinomadura
sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs
in silico
to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming
Actinomadura
sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future. |
doi_str_mv | 10.1007/s10295-019-02256-5 |
format | Article |
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Actinomadura
sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs
in silico
to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming
Actinomadura
sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.</description><identifier>ISSN: 1367-5435</identifier><identifier>EISSN: 1476-5535</identifier><identifier>DOI: 10.1007/s10295-019-02256-5</identifier><identifier>PMID: 31853778</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antibiotics ; Biochemistry ; Bioinformatics ; Biomedical and Life Sciences ; Biosynthesis ; Biotechnology ; Biotechnology & Applied Microbiology ; Coccidiosis ; Conjugation ; Drug dosages ; Fermentation ; Gene sequencing ; Genetic Engineering ; Genetics and Molecular Biology of Industrial Organisms - Original Paper ; Genomes ; Genomics ; Inorganic Chemistry ; Laboratories ; Life Sciences ; Life Sciences & Biomedicine ; Maduramicin ; Market shares ; Metabolic engineering ; Metabolism ; Microbiology ; Microorganisms ; Polyethers ; Science & Technology ; Thioesterase ; Whole genome sequencing</subject><ispartof>Journal of industrial microbiology & biotechnology, 2020-02, Vol.47 (2), p.275-285</ispartof><rights>Society for Industrial Microbiology and Biotechnology 2019</rights><rights>Journal of Industrial Microbiology and Biotechnology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>7</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000519382900010</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c456t-c10a7300e9a960a2f74a31f261cb20c6aa183d82615c0fca17b8d2d37b9d78643</citedby><cites>FETCH-LOGICAL-c456t-c10a7300e9a960a2f74a31f261cb20c6aa183d82615c0fca17b8d2d37b9d78643</cites><orcidid>0000-0002-9605-231X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10295-019-02256-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10295-019-02256-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,28257,41497,42566,51328</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31853778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Ran</creatorcontrib><creatorcontrib>Fang, Fang</creatorcontrib><creatorcontrib>An, Ziheng</creatorcontrib><creatorcontrib>Huang, Renqiong</creatorcontrib><creatorcontrib>Wang, Yong</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><creatorcontrib>Fu, Shuai</creatorcontrib><creatorcontrib>Fu, Aisi</creatorcontrib><creatorcontrib>Deng, Zixin</creatorcontrib><creatorcontrib>Liu, Tiangang</creatorcontrib><title>Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007</title><title>Journal of industrial microbiology & biotechnology</title><addtitle>J Ind Microbiol Biotechnol</addtitle><addtitle>J IND MICROBIOL BIOT</addtitle><addtitle>J Ind Microbiol Biotechnol</addtitle><description>Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of
Actinomadura
sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs
in silico
to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming
Actinomadura
sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.</description><subject>Antibiotics</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Biotechnology & Applied Microbiology</subject><subject>Coccidiosis</subject><subject>Conjugation</subject><subject>Drug dosages</subject><subject>Fermentation</subject><subject>Gene sequencing</subject><subject>Genetic Engineering</subject><subject>Genetics and Molecular Biology of Industrial Organisms - Original Paper</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Inorganic Chemistry</subject><subject>Laboratories</subject><subject>Life Sciences</subject><subject>Life Sciences & Biomedicine</subject><subject>Maduramicin</subject><subject>Market shares</subject><subject>Metabolic engineering</subject><subject>Metabolism</subject><subject>Microbiology</subject><subject>Microorganisms</subject><subject>Polyethers</subject><subject>Science & Technology</subject><subject>Thioesterase</subject><subject>Whole genome sequencing</subject><issn>1367-5435</issn><issn>1476-5535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><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>eNqNkU1rFTEYhYMotlb_gAsJuBHK1HxMJsmyXGy1FLqp65BJMjXlTnJNZlou_nnf6dQKLoqrnJDnvB85CL2n5IQSIj9XSpgWDaG6IYyJrhEv0CFtJQjBxUvQvJONaLk4QG9qvSWECCnZa3TAqRJcSnWIfp2HlMfoauNLvAsJ-1hdvgtlj_OApx8B9zHXfQI1RYdvQgrYbec6hbIAo_VzseCPCdvkcZwqXty7kv3sppgThpdTUNDlgcV1d4IvaAMLvEWvBrut4d3jeYS-n3253nxtLq_Ov21OLxvXim5qHCVWckKCtrojlg2ytZwOrKOuZ8R11lLFvYK7cGRwlspeeea57LWXqmv5Efq01oWpfs6hTmaEJcN2a1PIczWMMyVbrQkH9OM_6G2eS4LpgOq4pFqoDii2Uq7kWksYzK7E0Za9ocQs0Zg1GgPRmIdojADTh8fScz8G_2T5kwUAagXuQ5-H6mJILjxhS3hUc8U0KEo2cbLL927ynCawHv-_FWi-0hWIdBPK3yWfmf83zoy6KQ</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Liu, Ran</creator><creator>Fang, Fang</creator><creator>An, Ziheng</creator><creator>Huang, Renqiong</creator><creator>Wang, Yong</creator><creator>Sun, Xiao</creator><creator>Fu, Shuai</creator><creator>Fu, Aisi</creator><creator>Deng, Zixin</creator><creator>Liu, Tiangang</creator><general>Springer International Publishing</general><general>Springer Nature</general><general>Oxford University Press</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7WY</scope><scope>7WZ</scope><scope>7X7</scope><scope>7XB</scope><scope>87Z</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FL</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FRNLG</scope><scope>FYUFA</scope><scope>F~G</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K60</scope><scope>K6~</scope><scope>K9.</scope><scope>L.-</scope><scope>LK8</scope><scope>M0C</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9605-231X</orcidid></search><sort><creationdate>20200201</creationdate><title>Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007</title><author>Liu, Ran ; Fang, Fang ; An, Ziheng ; Huang, Renqiong ; Wang, Yong ; Sun, Xiao ; Fu, Shuai ; Fu, Aisi ; Deng, Zixin ; Liu, Tiangang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-c10a7300e9a960a2f74a31f261cb20c6aa183d82615c0fca17b8d2d37b9d78643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibiotics</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>Biotechnology</topic><topic>Biotechnology & Applied Microbiology</topic><topic>Coccidiosis</topic><topic>Conjugation</topic><topic>Drug dosages</topic><topic>Fermentation</topic><topic>Gene sequencing</topic><topic>Genetic Engineering</topic><topic>Genetics and Molecular Biology of Industrial Organisms - Original Paper</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Inorganic Chemistry</topic><topic>Laboratories</topic><topic>Life Sciences</topic><topic>Life Sciences & Biomedicine</topic><topic>Maduramicin</topic><topic>Market shares</topic><topic>Metabolic engineering</topic><topic>Metabolism</topic><topic>Microbiology</topic><topic>Microorganisms</topic><topic>Polyethers</topic><topic>Science & Technology</topic><topic>Thioesterase</topic><topic>Whole genome sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Ran</creatorcontrib><creatorcontrib>Fang, Fang</creatorcontrib><creatorcontrib>An, Ziheng</creatorcontrib><creatorcontrib>Huang, Renqiong</creatorcontrib><creatorcontrib>Wang, Yong</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><creatorcontrib>Fu, Shuai</creatorcontrib><creatorcontrib>Fu, Aisi</creatorcontrib><creatorcontrib>Deng, Zixin</creatorcontrib><creatorcontrib>Liu, Tiangang</creatorcontrib><collection>Web of Science - 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Academic</collection><jtitle>Journal of industrial microbiology & biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Ran</au><au>Fang, Fang</au><au>An, Ziheng</au><au>Huang, Renqiong</au><au>Wang, Yong</au><au>Sun, Xiao</au><au>Fu, Shuai</au><au>Fu, Aisi</au><au>Deng, Zixin</au><au>Liu, Tiangang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007</atitle><jtitle>Journal of industrial microbiology & biotechnology</jtitle><stitle>J Ind Microbiol Biotechnol</stitle><stitle>J IND MICROBIOL BIOT</stitle><addtitle>J Ind Microbiol Biotechnol</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>47</volume><issue>2</issue><spage>275</spage><epage>285</epage><pages>275-285</pages><issn>1367-5435</issn><eissn>1476-5535</eissn><abstract>Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of
Actinomadura
sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs
in silico
to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming
Actinomadura
sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>31853778</pmid><doi>10.1007/s10295-019-02256-5</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-9605-231X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antibiotics Biochemistry Bioinformatics Biomedical and Life Sciences Biosynthesis Biotechnology Biotechnology & Applied Microbiology Coccidiosis Conjugation Drug dosages Fermentation Gene sequencing Genetic Engineering Genetics and Molecular Biology of Industrial Organisms - Original Paper Genomes Genomics Inorganic Chemistry Laboratories Life Sciences Life Sciences & Biomedicine Maduramicin Market shares Metabolic engineering Metabolism Microbiology Microorganisms Polyethers Science & Technology Thioesterase Whole genome sequencing |
title | Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007 |
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