Co‐overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis

Aims To improve lincomycin A production and decrease the content of byproduct lincomycin B in an industrial lincomycin‐producing strain. Methods and Results The in silico analysis indicated that LmbW could be involved in propylproline biosynthesis of lincomyin A. In this study, we constructed an lmb...

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Veröffentlicht in:Journal of applied microbiology 2015-10, Vol.119 (4), p.1064-1074
Hauptverfasser: Pang, A.‐P., Du, L., Lin, C.‐Y., Qiao, J., Zhao, G.‐R.
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container_end_page 1074
container_issue 4
container_start_page 1064
container_title Journal of applied microbiology
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creator Pang, A.‐P.
Du, L.
Lin, C.‐Y.
Qiao, J.
Zhao, G.‐R.
description Aims To improve lincomycin A production and decrease the content of byproduct lincomycin B in an industrial lincomycin‐producing strain. Methods and Results The in silico analysis indicated that LmbW could be involved in propylproline biosynthesis of lincomyin A. In this study, we constructed an lmbW deletion mutant and found that the mutant lost the ability to produce lincomycin A, but increased the accumulation of lincomycin B. The loss of lincomycin A production can be restored by complementing the mutant with the expression of lmbW gene. When lmbW and metK (encoding S‐adenosylmethionine synthetase) was co‐overexpressed, lincomycin A titre was 1744·6 mg l−1, a 35·83% improvement over the original strain. Meanwhile, the content of lincomycin B was reduced to 4·41%, a remarkable decrease of 34·76%, compared to that of the original strain. Conclusions lmbW encodes a C‐methyltransferase involved in the biosynthesis of lincomycin A but not lincomycin B. Co‐overexpression of lmbW and metK improved lincomycin A production and decreased the content of lincomycin B. Significance and Impact of the Study The engineered Streptomyces lincolnensis strain shows promising application in the fermentation production of lincomycin A, which may help cut production costs and simplify downstream separation processes.
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Methods and Results The in silico analysis indicated that LmbW could be involved in propylproline biosynthesis of lincomyin A. In this study, we constructed an lmbW deletion mutant and found that the mutant lost the ability to produce lincomycin A, but increased the accumulation of lincomycin B. The loss of lincomycin A production can be restored by complementing the mutant with the expression of lmbW gene. When lmbW and metK (encoding S‐adenosylmethionine synthetase) was co‐overexpressed, lincomycin A titre was 1744·6 mg l−1, a 35·83% improvement over the original strain. Meanwhile, the content of lincomycin B was reduced to 4·41%, a remarkable decrease of 34·76%, compared to that of the original strain. Conclusions lmbW encodes a C‐methyltransferase involved in the biosynthesis of lincomycin A but not lincomycin B. Co‐overexpression of lmbW and metK improved lincomycin A production and decreased the content of lincomycin B. Significance and Impact of the Study The engineered Streptomyces lincolnensis strain shows promising application in the fermentation production of lincomycin A, which may help cut production costs and simplify downstream separation processes.</description><identifier>ISSN: 1364-5072</identifier><identifier>EISSN: 1365-2672</identifier><identifier>DOI: 10.1111/jam.12919</identifier><identifier>PMID: 26248490</identifier><identifier>CODEN: JAMIFK</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Bioengineering ; Biosynthesis ; Biotechnology ; Fermentation ; lincomycin ; Lincomycin - biosynthesis ; Lincosamides - biosynthesis ; lmbW ; metabolic engineering ; Methionine Adenosyltransferase - metabolism ; methyltransferase ; Microbiology ; Molecular Sequence Data ; Streptomyces - genetics ; Streptomyces - metabolism ; Streptomyces lincolnensis ; synthetic biology</subject><ispartof>Journal of applied microbiology, 2015-10, Vol.119 (4), p.1064-1074</ispartof><rights>2015 The Society for Applied Microbiology</rights><rights>2015 The Society for Applied Microbiology.</rights><rights>Copyright © 2015 The Society for Applied Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4219-cc56b25d4ab3ab48e50d28a449443d1f116a95e7e5c0557c9843acc7210a0c903</citedby><cites>FETCH-LOGICAL-c4219-cc56b25d4ab3ab48e50d28a449443d1f116a95e7e5c0557c9843acc7210a0c903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjam.12919$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjam.12919$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26248490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pang, A.‐P.</creatorcontrib><creatorcontrib>Du, L.</creatorcontrib><creatorcontrib>Lin, C.‐Y.</creatorcontrib><creatorcontrib>Qiao, J.</creatorcontrib><creatorcontrib>Zhao, G.‐R.</creatorcontrib><title>Co‐overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis</title><title>Journal of applied microbiology</title><addtitle>J Appl Microbiol</addtitle><description>Aims To improve lincomycin A production and decrease the content of byproduct lincomycin B in an industrial lincomycin‐producing strain. Methods and Results The in silico analysis indicated that LmbW could be involved in propylproline biosynthesis of lincomyin A. In this study, we constructed an lmbW deletion mutant and found that the mutant lost the ability to produce lincomycin A, but increased the accumulation of lincomycin B. The loss of lincomycin A production can be restored by complementing the mutant with the expression of lmbW gene. When lmbW and metK (encoding S‐adenosylmethionine synthetase) was co‐overexpressed, lincomycin A titre was 1744·6 mg l−1, a 35·83% improvement over the original strain. Meanwhile, the content of lincomycin B was reduced to 4·41%, a remarkable decrease of 34·76%, compared to that of the original strain. Conclusions lmbW encodes a C‐methyltransferase involved in the biosynthesis of lincomycin A but not lincomycin B. Co‐overexpression of lmbW and metK improved lincomycin A production and decreased the content of lincomycin B. Significance and Impact of the Study The engineered Streptomyces lincolnensis strain shows promising application in the fermentation production of lincomycin A, which may help cut production costs and simplify downstream separation processes.</description><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Bioengineering</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Fermentation</subject><subject>lincomycin</subject><subject>Lincomycin - biosynthesis</subject><subject>Lincosamides - biosynthesis</subject><subject>lmbW</subject><subject>metabolic engineering</subject><subject>Methionine Adenosyltransferase - metabolism</subject><subject>methyltransferase</subject><subject>Microbiology</subject><subject>Molecular Sequence Data</subject><subject>Streptomyces - genetics</subject><subject>Streptomyces - metabolism</subject><subject>Streptomyces lincolnensis</subject><subject>synthetic biology</subject><issn>1364-5072</issn><issn>1365-2672</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2KFDEUhYMozji68AUk4EYXNZPfSmXZNv6PuFBxWaRSt6GaVNImKbV3PsK8ybyTT2Kqq0dEEMwi94Z851wuB6GHlJzTci62ZjynTFN9C51SXsuK1YrdPvSikkSxE3QvpS0hlBNZ30UnrGaiEZqcout1-PnjKnyFCN93EVIagsdhg93YfcbG93iE_BY76HEOePA2gknl4Uobxr0dPF7hXQz9ZPOsnBU93FDd_vj1J_8M2-Az-FzsCl_ufko5DsbhUsxwGP8hR9jlWQFpETsPPg3pPrqzMS7Bg2M9Q59ePP-4flVdvn_5er26rKxgVFfWyrpjshem46YTDUjSs8YIoYXgPd1QWhstQYG0REpldSO4sVYxSgyxmvAz9GTxLRt8mSDldhySBeeMhzCllqpG6YYyJf8DpbKWmite0Md_odswRV8WmSmuZa20LtTThbIxpBRh0-7iMJq4bylp58DbEnh7CLywj46OUzdC_5u8SbgAFwvwbXCw_7dT-2b1brH8BRx4uEU</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Pang, A.‐P.</creator><creator>Du, L.</creator><creator>Lin, C.‐Y.</creator><creator>Qiao, J.</creator><creator>Zhao, G.‐R.</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7ST</scope><scope>SOI</scope></search><sort><creationdate>201510</creationdate><title>Co‐overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis</title><author>Pang, A.‐P. ; 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source MEDLINE; Oxford University Press Journals All Titles (1996-Current); Wiley Online Library All Journals
subjects Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bioengineering
Biosynthesis
Biotechnology
Fermentation
lincomycin
Lincomycin - biosynthesis
Lincosamides - biosynthesis
lmbW
metabolic engineering
Methionine Adenosyltransferase - metabolism
methyltransferase
Microbiology
Molecular Sequence Data
Streptomyces - genetics
Streptomyces - metabolism
Streptomyces lincolnensis
synthetic biology
title Co‐overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis
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