Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis
Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Strepto...
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| creator | Xu, Yurong Tang, Yaqian Wang, Nian Liu, Jing Cai, Xinlu Cai, Hongyi Li, Jie Tan, Guoqing Liu, Ruihua Bai, Linquan Zhang, Lixin Wu, Hang Zhang, Buchang |
| description | Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in
Streptomyces lincolnensis
, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (
lmbA
and
lmbV
), three resistance genes (
lmrA
,
lmrB
and
lmrC
), and a regulatory gene (
lmbU
) within the lincomycin biosynthetic gene (
lin
) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene
SLCG_3127
encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of
SLCG_3127
and
SLCG_Lrp
was precisely identified. Inactivation of
SLCG_3127
in
S. lincolnensis
resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside
lin
cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation. |
| doi_str_mv | 10.1007/s00253-020-10381-w |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2364922141</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A615423939</galeid><sourcerecordid>A615423939</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-1766d1aaa444f8e15c0ae9d90c657ba207465261893f8d9221efc8a94d0d7be13</originalsourceid><addsrcrecordid>eNp9kl2L1TAQhoMo7vHoH_BCAl550TVfTdvLZfFjYUFw1-uQk05rljapSbprf4d_2NTuqgdEAgmTed4JM3kReknJKSWkehsJYSUvCCMFJbymxd0jtKOCs4JIKh6jHaFVWVRlU5-gZzHeEEJZLeVTdMJp0_CK0B36cR20iybYKVnv9IAD9POg1wD7Dms8wGysgyJAnLyL9hYeEB8WPAWfwDrc-YBbG8CkYcHGuxT8MFjX47wZPy65BD5YHxeXvkK0Eef4KgWY0pqEuHGDg_xCfI6edHqI8OL-3KMv799dn38sLj99uDg_uyxMSXkqaCVlS7XWQoiuBloaoqFpG2JkWR00I5WQJZO0bnhXtw1jFDpT60a0pK0OQPkevd7q5i6-zRCTuvFzyEOIinEpVoX4i-r1AMq6zqegzWijUWeSloLxJq89Ov0HlVcLo80Dgc7m-yPBmyPBOjT4nno9x6gurj4fs2xjTfAxBujUFOyow6IoUasV1GYFla2gfllB3WXRq_vu5sMI7W_Jw99ngG9AzCnXQ_jT_n_K_gTyY8HW</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2364922141</pqid></control><display><type>article</type><title>Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis</title><source>Springer Nature - Complete Springer Journals</source><creator>Xu, Yurong ; Tang, Yaqian ; Wang, Nian ; Liu, Jing ; Cai, Xinlu ; Cai, Hongyi ; Li, Jie ; Tan, Guoqing ; Liu, Ruihua ; Bai, Linquan ; Zhang, Lixin ; Wu, Hang ; Zhang, Buchang</creator><creatorcontrib>Xu, Yurong ; Tang, Yaqian ; Wang, Nian ; Liu, Jing ; Cai, Xinlu ; Cai, Hongyi ; Li, Jie ; Tan, Guoqing ; Liu, Ruihua ; Bai, Linquan ; Zhang, Lixin ; Wu, Hang ; Zhang, Buchang</creatorcontrib><description>Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in
Streptomyces lincolnensis
, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (
lmbA
and
lmbV
), three resistance genes (
lmrA
,
lmrB
and
lmrC
), and a regulatory gene (
lmbU
) within the lincomycin biosynthetic gene (
lin
) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene
SLCG_3127
encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of
SLCG_3127
and
SLCG_Lrp
was precisely identified. Inactivation of
SLCG_3127
in
S. lincolnensis
resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside
lin
cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.</description><identifier>ISSN: 0175-7598</identifier><identifier>EISSN: 1432-0614</identifier><identifier>DOI: 10.1007/s00253-020-10381-w</identifier><identifier>PMID: 31993701</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Actinomycetes ; Antibiotics ; Applied Genetics and Molecular Biotechnology ; Arginine ; Binding sites ; Biological activity ; Biomedical and Life Sciences ; Biosynthesis ; Biotechnology ; Blood proteins ; Clusters ; Cysteine ; Deactivation ; Deoxyribonucleic acid ; DNA ; DNA binding proteins ; Ethylenediaminetetraacetic acid ; Gene expression ; Gene regulation ; Genes ; Genetic aspects ; Genetic transcription ; Inactivation ; Leucine ; Life Sciences ; Lincomycin ; Microbial Genetics and Genomics ; Microbiology ; Molecular modelling ; Phenylalanine ; Proline ; Protein binding ; Proteins ; Regulatory proteins ; Spiramycin ; Streptomyces ; Transcription factors</subject><ispartof>Applied microbiology and biotechnology, 2020-03, Vol.104 (6), p.2575-2587</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-1766d1aaa444f8e15c0ae9d90c657ba207465261893f8d9221efc8a94d0d7be13</citedby><cites>FETCH-LOGICAL-c513t-1766d1aaa444f8e15c0ae9d90c657ba207465261893f8d9221efc8a94d0d7be13</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/s00253-020-10381-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00253-020-10381-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31993701$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Yurong</creatorcontrib><creatorcontrib>Tang, Yaqian</creatorcontrib><creatorcontrib>Wang, Nian</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Cai, Xinlu</creatorcontrib><creatorcontrib>Cai, Hongyi</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Tan, Guoqing</creatorcontrib><creatorcontrib>Liu, Ruihua</creatorcontrib><creatorcontrib>Bai, Linquan</creatorcontrib><creatorcontrib>Zhang, Lixin</creatorcontrib><creatorcontrib>Wu, Hang</creatorcontrib><creatorcontrib>Zhang, Buchang</creatorcontrib><title>Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis</title><title>Applied microbiology and biotechnology</title><addtitle>Appl Microbiol Biotechnol</addtitle><addtitle>Appl Microbiol Biotechnol</addtitle><description>Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in
Streptomyces lincolnensis
, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (
lmbA
and
lmbV
), three resistance genes (
lmrA
,
lmrB
and
lmrC
), and a regulatory gene (
lmbU
) within the lincomycin biosynthetic gene (
lin
) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene
SLCG_3127
encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of
SLCG_3127
and
SLCG_Lrp
was precisely identified. Inactivation of
SLCG_3127
in
S. lincolnensis
resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside
lin
cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.</description><subject>Actinomycetes</subject><subject>Antibiotics</subject><subject>Applied Genetics and Molecular Biotechnology</subject><subject>Arginine</subject><subject>Binding sites</subject><subject>Biological activity</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Blood proteins</subject><subject>Clusters</subject><subject>Cysteine</subject><subject>Deactivation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Inactivation</subject><subject>Leucine</subject><subject>Life Sciences</subject><subject>Lincomycin</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>Molecular modelling</subject><subject>Phenylalanine</subject><subject>Proline</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Regulatory proteins</subject><subject>Spiramycin</subject><subject>Streptomyces</subject><subject>Transcription factors</subject><issn>0175-7598</issn><issn>1432-0614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kl2L1TAQhoMo7vHoH_BCAl550TVfTdvLZfFjYUFw1-uQk05rljapSbprf4d_2NTuqgdEAgmTed4JM3kReknJKSWkehsJYSUvCCMFJbymxd0jtKOCs4JIKh6jHaFVWVRlU5-gZzHeEEJZLeVTdMJp0_CK0B36cR20iybYKVnv9IAD9POg1wD7Dms8wGysgyJAnLyL9hYeEB8WPAWfwDrc-YBbG8CkYcHGuxT8MFjX47wZPy65BD5YHxeXvkK0Eef4KgWY0pqEuHGDg_xCfI6edHqI8OL-3KMv799dn38sLj99uDg_uyxMSXkqaCVlS7XWQoiuBloaoqFpG2JkWR00I5WQJZO0bnhXtw1jFDpT60a0pK0OQPkevd7q5i6-zRCTuvFzyEOIinEpVoX4i-r1AMq6zqegzWijUWeSloLxJq89Ov0HlVcLo80Dgc7m-yPBmyPBOjT4nno9x6gurj4fs2xjTfAxBujUFOyow6IoUasV1GYFla2gfllB3WXRq_vu5sMI7W_Jw99ngG9AzCnXQ_jT_n_K_gTyY8HW</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Xu, Yurong</creator><creator>Tang, Yaqian</creator><creator>Wang, Nian</creator><creator>Liu, Jing</creator><creator>Cai, Xinlu</creator><creator>Cai, 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regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis</title><author>Xu, Yurong ; Tang, Yaqian ; Wang, Nian ; Liu, Jing ; Cai, Xinlu ; Cai, Hongyi ; Li, Jie ; Tan, Guoqing ; Liu, Ruihua ; Bai, Linquan ; Zhang, Lixin ; Wu, Hang ; Zhang, Buchang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-1766d1aaa444f8e15c0ae9d90c657ba207465261893f8d9221efc8a94d0d7be13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Actinomycetes</topic><topic>Antibiotics</topic><topic>Applied Genetics and Molecular Biotechnology</topic><topic>Arginine</topic><topic>Binding sites</topic><topic>Biological activity</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>Biotechnology</topic><topic>Blood proteins</topic><topic>Clusters</topic><topic>Cysteine</topic><topic>Deactivation</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA binding proteins</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Inactivation</topic><topic>Leucine</topic><topic>Life Sciences</topic><topic>Lincomycin</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Molecular modelling</topic><topic>Phenylalanine</topic><topic>Proline</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Regulatory proteins</topic><topic>Spiramycin</topic><topic>Streptomyces</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Yurong</creatorcontrib><creatorcontrib>Tang, Yaqian</creatorcontrib><creatorcontrib>Wang, 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Yurong</au><au>Tang, Yaqian</au><au>Wang, Nian</au><au>Liu, Jing</au><au>Cai, Xinlu</au><au>Cai, Hongyi</au><au>Li, Jie</au><au>Tan, Guoqing</au><au>Liu, Ruihua</au><au>Bai, Linquan</au><au>Zhang, Lixin</au><au>Wu, Hang</au><au>Zhang, Buchang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis</atitle><jtitle>Applied microbiology and biotechnology</jtitle><stitle>Appl Microbiol Biotechnol</stitle><addtitle>Appl Microbiol Biotechnol</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>104</volume><issue>6</issue><spage>2575</spage><epage>2587</epage><pages>2575-2587</pages><issn>0175-7598</issn><eissn>1432-0614</eissn><abstract>Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in
Streptomyces lincolnensis
, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (
lmbA
and
lmbV
), three resistance genes (
lmrA
,
lmrB
and
lmrC
), and a regulatory gene (
lmbU
) within the lincomycin biosynthetic gene (
lin
) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene
SLCG_3127
encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of
SLCG_3127
and
SLCG_Lrp
was precisely identified. Inactivation of
SLCG_3127
in
S. lincolnensis
resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside
lin
cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31993701</pmid><doi>10.1007/s00253-020-10381-w</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0175-7598 |
| ispartof | Applied microbiology and biotechnology, 2020-03, Vol.104 (6), p.2575-2587 |
| issn | 0175-7598 1432-0614 |
| language | eng |
| recordid | cdi_proquest_journals_2364922141 |
| source | Springer Nature - Complete Springer Journals |
| subjects | Actinomycetes Antibiotics Applied Genetics and Molecular Biotechnology Arginine Binding sites Biological activity Biomedical and Life Sciences Biosynthesis Biotechnology Blood proteins Clusters Cysteine Deactivation Deoxyribonucleic acid DNA DNA binding proteins Ethylenediaminetetraacetic acid Gene expression Gene regulation Genes Genetic aspects Genetic transcription Inactivation Leucine Life Sciences Lincomycin Microbial Genetics and Genomics Microbiology Molecular modelling Phenylalanine Proline Protein binding Proteins Regulatory proteins Spiramycin Streptomyces Transcription factors |
| title | Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis |
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