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The LuxR family members GdmRI and GdmRII are positive regulators of geldanamycin biosynthesis in Streptomyces hygroscopicus 17997

Identifieur interne : 001101 ( Istex/Corpus ); précédent : 001100; suivant : 001102

The LuxR family members GdmRI and GdmRII are positive regulators of geldanamycin biosynthesis in Streptomyces hygroscopicus 17997

Auteurs : Weiqing He ; Jian Lei ; Yuying Liu ; Yiguang Wang

Source :

RBID : ISTEX:F7752652196076C6A08343BF978E783F01412A8F

English descriptors

Abstract

Abstract: The recent sequencing of the DNA region of the geldanamycin post-polyketide synthase (PKS) modification gene clusters revealed the presence of two regulatory genes: gdmRI (2,907 bp) and gdmRII (2,766 bp). The deduced products of gdmRI and gdmRII (968 and 921 amino acid residues, respectively) were identified as homologues of the LuxR transcriptional regulatory proteins. Inactivation by gene replacement of gdmRI or gdmRII in the Streptomyces hygroscopicus 17997 genome resulted in a complete loss of geldanamycin production. Complementation by a plasmid carrying gdmRI or gdmRII restored geldanamycin production, suggesting that the products of these two regulatory genes are positive regulators that are required for geldanamycin biosynthesis. The gdmRI transcript was detected in the ΔgdmRII mutant, and the gdmRII was detected in the ΔgdmRI mutant, indicating that the two genes are transcribed independently and do not regulate each other. Time course of gene expression analysis by RT-PCR of the geldanamycin biosynthetic genes showed that the transcription of gdmRI and gdmRII correlates with that of genes involved in polyketide biosynthesis, but not with the post-PKS modification gene gdmN, whose transcription is initiated earlier. gdmRI or gdmRII gene disruptants did not transcribe the polyketide biosynthetic related genes pks, gdmF, and gdnA-O-P, but did trancribe gdmN. These results demonstrated that gdmRI and gdmRII are pathway-specific positive regulators that control the polyketide biosynthetic genes in geldanamycin biosynthsis, but not the post-PKS modification gene, gdmN.

Url:
DOI: 10.1007/s00203-007-0346-2

Links to Exploration step

ISTEX:F7752652196076C6A08343BF978E783F01412A8F

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<Revised>
<Year>2007</Year>
<Month>10</Month>
<Day>17</Day>
</Revised>
<Accepted>
<Year>2007</Year>
<Month>12</Month>
<Day>11</Day>
</Accepted>
<OnlineDate>
<Year>2008</Year>
<Month>1</Month>
<Day>24</Day>
</OnlineDate>
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<ArticleEditorialResponsibility>Jean-Luc Pernodet</ArticleEditorialResponsibility>
<ArticleCopyright>
<CopyrightHolderName>Springer-Verlag</CopyrightHolderName>
<CopyrightYear>2008</CopyrightYear>
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<ArticleHeader>
<AuthorGroup>
<Author AffiliationIDS="Aff1">
<AuthorName DisplayOrder="Western">
<GivenName>Weiqing</GivenName>
<FamilyName>He</FamilyName>
</AuthorName>
</Author>
<Author AffiliationIDS="Aff1">
<AuthorName DisplayOrder="Western">
<GivenName>Jian</GivenName>
<FamilyName>Lei</FamilyName>
</AuthorName>
</Author>
<Author AffiliationIDS="Aff1">
<AuthorName DisplayOrder="Western">
<GivenName>Yuying</GivenName>
<FamilyName>Liu</FamilyName>
</AuthorName>
</Author>
<Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1">
<AuthorName DisplayOrder="Western">
<GivenName>Yiguang</GivenName>
<FamilyName>Wang</FamilyName>
</AuthorName>
<Contact>
<Phone>+86-10-63038137</Phone>
<Fax>+86-10-63176489</Fax>
<Email>wangyh456@yahoo.com.cn</Email>
</Contact>
</Author>
<Affiliation ID="Aff1">
<OrgDivision>Key Laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology</OrgDivision>
<OrgName>Chinese Academy of Medical Sciences, Peking Union Medical College</OrgName>
<OrgAddress>
<City>Beijing</City>
<Postcode>100050</Postcode>
<Country Code="CN">China</Country>
</OrgAddress>
</Affiliation>
</AuthorGroup>
<Abstract ID="Abs1" Language="En" OutputMedium="All">
<Heading>Abstract</Heading>
<Para>The recent sequencing of the DNA region of the geldanamycin post-polyketide synthase (PKS) modification gene clusters revealed the presence of two regulatory genes:
<Emphasis Type="Italic">gdmRI</Emphasis>
(2,907 bp) and
<Emphasis Type="Italic">gdmRII</Emphasis>
(2,766 bp). The deduced products of
<Emphasis Type="Italic">gdmRI</Emphasis>
and
<Emphasis Type="Italic">gdmRII</Emphasis>
(968 and 921 amino acid residues, respectively) were identified as homologues of the LuxR transcriptional regulatory proteins. Inactivation by gene replacement of
<Emphasis Type="Italic">gdmRI</Emphasis>
or
<Emphasis Type="Italic">gdmRII</Emphasis>
in the
<Emphasis Type="Italic">Streptomyces hygroscopicus</Emphasis>
17997 genome resulted in a complete loss of geldanamycin production. Complementation by a plasmid carrying
<Emphasis Type="Italic">gdmRI</Emphasis>
or
<Emphasis Type="Italic">gdmRII</Emphasis>
restored geldanamycin production, suggesting that the products of these two regulatory genes are positive regulators that are required for geldanamycin biosynthesis. The
<Emphasis Type="Italic">gdmRI</Emphasis>
transcript was detected in the Δ
<Emphasis Type="Italic">gdmRII</Emphasis>
mutant, and the
<Emphasis Type="Italic">gdm</Emphasis>
RII was detected in the Δ
<Emphasis Type="Italic">gdmRI</Emphasis>
mutant, indicating that the two genes are transcribed independently and do not regulate each other. Time course of gene expression analysis by RT-PCR of the geldanamycin biosynthetic genes showed that the transcription of
<Emphasis Type="Italic">gdmRI</Emphasis>
and
<Emphasis Type="Italic">gdmRII</Emphasis>
correlates with that of genes involved in polyketide biosynthesis, but not with the post-PKS modification gene
<Emphasis Type="Italic">gdmN</Emphasis>
, whose transcription is initiated earlier.
<Emphasis Type="Italic">gdmRI</Emphasis>
or
<Emphasis Type="Italic">gdmRII</Emphasis>
gene disruptants did not transcribe the polyketide biosynthetic related genes
<Emphasis Type="Italic">pks, gdmF</Emphasis>
, and
<Emphasis Type="Italic">gdnA-O-P</Emphasis>
, but did trancribe
<Emphasis Type="Italic">gdmN</Emphasis>
. These results demonstrated that
<Emphasis Type="Italic">gdmRI</Emphasis>
and
<Emphasis Type="Italic">gdmRII</Emphasis>
are pathway-specific positive regulators that control the polyketide biosynthetic genes in geldanamycin biosynthsis, but not the post-PKS modification gene,
<Emphasis Type="Italic">gdmN.</Emphasis>
</Para>
</Abstract>
<KeywordGroup Language="En" OutputMedium="All">
<Heading>Keywords</Heading>
<Keyword>Geldanamycin biosynthesis</Keyword>
<Keyword>Positive regulator</Keyword>
<Keyword>Lux R family members</Keyword>
</KeywordGroup>
<ArticleNote Type="CommunicatedBy">
<SimplePara>Communicated by Jean-Luc Pernodet.</SimplePara>
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<title>The LuxR family members GdmRI and GdmRII are positive regulators of geldanamycin biosynthesis in Streptomyces hygroscopicus 17997</title>
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<title>The LuxR family members GdmRI and GdmRII are positive regulators of geldanamycin biosynthesis in Streptomyces hygroscopicus 17997</title>
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<name type="personal">
<namePart type="given">Weiqing</namePart>
<namePart type="family">He</namePart>
<affiliation>Key Laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, 100050, Beijing, China</affiliation>
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<namePart type="given">Jian</namePart>
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<affiliation>Key Laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, 100050, Beijing, China</affiliation>
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<roleTerm type="text">author</roleTerm>
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<name type="personal">
<namePart type="given">Yuying</namePart>
<namePart type="family">Liu</namePart>
<affiliation>Key Laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, 100050, Beijing, China</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
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<name type="personal" displayLabel="corresp">
<namePart type="given">Yiguang</namePart>
<namePart type="family">Wang</namePart>
<affiliation>Key Laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, 100050, Beijing, China</affiliation>
<affiliation>E-mail: wangyh456@yahoo.com.cn</affiliation>
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<abstract lang="en">Abstract: The recent sequencing of the DNA region of the geldanamycin post-polyketide synthase (PKS) modification gene clusters revealed the presence of two regulatory genes: gdmRI (2,907 bp) and gdmRII (2,766 bp). The deduced products of gdmRI and gdmRII (968 and 921 amino acid residues, respectively) were identified as homologues of the LuxR transcriptional regulatory proteins. Inactivation by gene replacement of gdmRI or gdmRII in the Streptomyces hygroscopicus 17997 genome resulted in a complete loss of geldanamycin production. Complementation by a plasmid carrying gdmRI or gdmRII restored geldanamycin production, suggesting that the products of these two regulatory genes are positive regulators that are required for geldanamycin biosynthesis. The gdmRI transcript was detected in the ΔgdmRII mutant, and the gdmRII was detected in the ΔgdmRI mutant, indicating that the two genes are transcribed independently and do not regulate each other. Time course of gene expression analysis by RT-PCR of the geldanamycin biosynthetic genes showed that the transcription of gdmRI and gdmRII correlates with that of genes involved in polyketide biosynthesis, but not with the post-PKS modification gene gdmN, whose transcription is initiated earlier. gdmRI or gdmRII gene disruptants did not transcribe the polyketide biosynthetic related genes pks, gdmF, and gdnA-O-P, but did trancribe gdmN. These results demonstrated that gdmRI and gdmRII are pathway-specific positive regulators that control the polyketide biosynthetic genes in geldanamycin biosynthsis, but not the post-PKS modification gene, gdmN.</abstract>
<note>Original Paper</note>
<subject lang="en">
<genre>Keywords</genre>
<topic>Geldanamycin biosynthesis</topic>
<topic>Positive regulator</topic>
<topic>Lux R family members</topic>
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<identifier type="ISSN">0302-8933</identifier>
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<identifier type="DOI">10.1007/s00203-007-0346-2</identifier>
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