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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Veröffentlicht in:Journal of industrial microbiology & biotechnology 2020-02, Vol.47 (2), p.275-285
Hauptverfasser: Liu, Ran, Fang, Fang, An, Ziheng, Huang, Renqiong, Wang, Yong, Sun, Xiao, Fu, Shuai, Fu, Aisi, Deng, Zixin, Liu, Tiangang
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container_issue 2
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container_title Journal of industrial microbiology & biotechnology
container_volume 47
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
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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. 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J1-007</title><title>Journal of industrial microbiology &amp; 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 &amp; 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 &amp; 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 &amp; 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. 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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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