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Combinatorial Optimization of Resveratrol Production in Engineered E. coli.

Identifieur interne : 000130 ( Main/Exploration ); précédent : 000129; suivant : 000131

Combinatorial Optimization of Resveratrol Production in Engineered E. coli.

Auteurs : Ying Zhao [République populaire de Chine] ; Bi-Han Wu [République populaire de Chine] ; Zhen-Ning Liu [République populaire de Chine] ; Jianjun Qiao [République populaire de Chine] ; Guang-Rong Zhao [République populaire de Chine]

Source :

RBID : pubmed:30488696

Descripteurs français

English descriptors

Abstract

Resveratrol, a plant-derived polyphenolic compound with various health activities, is widely used in nutraceutical and food additives. Herein, combinatorial optimization of resveratrol biosynthetic pathway and intracellular environment of E. coli was carried out. By screening pathway genes from various species and exploring their expression pattern, we initially constructed resveratrol-producing strains. Further targeting at availability of malonyl-CoA through expressing ACC of Corynebacterium glutamicum and antisense inhibiting native fabD significantly increased resveratrol biosynthesis. Transport engineering for resveratrol secretion and molecular chaperones helping for folding heterologous enzymes were employed to improve the intracellular environments in remarkable degrees. By introducing PcTAL of Phanerochaete chrysosporium and tuning expression model of PcTAL, At4CL, and VvSTS, an engineered E. coli produced 57.77 mg/L of resveratrol from l-tyrosine. After integrating the above strategies, resveratrol titer reached to 238.71 mg/L from l-tyrosine. The combinatorial optimization in this study provides a promising strategy to produce valuable natural products in heterologous expression systems.

DOI: 10.1021/acs.jafc.8b05014
PubMed: 30488696


Affiliations:


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Le document en format XML

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<term>Corynebacterium glutamicum (genetics)</term>
<term>Corynebacterium glutamicum (metabolism)</term>
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<div type="abstract" xml:lang="en">Resveratrol, a plant-derived polyphenolic compound with various health activities, is widely used in nutraceutical and food additives. Herein, combinatorial optimization of resveratrol biosynthetic pathway and intracellular environment of E. coli was carried out. By screening pathway genes from various species and exploring their expression pattern, we initially constructed resveratrol-producing strains. Further targeting at availability of malonyl-CoA through expressing ACC of Corynebacterium glutamicum and antisense inhibiting native fabD significantly increased resveratrol biosynthesis. Transport engineering for resveratrol secretion and molecular chaperones helping for folding heterologous enzymes were employed to improve the intracellular environments in remarkable degrees. By introducing PcTAL of Phanerochaete chrysosporium and tuning expression model of PcTAL, At4CL, and VvSTS, an engineered E. coli produced 57.77 mg/L of resveratrol from l-tyrosine. After integrating the above strategies, resveratrol titer reached to 238.71 mg/L from l-tyrosine. The combinatorial optimization in this study provides a promising strategy to produce valuable natural products in heterologous expression systems.</div>
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<LastName>Liu</LastName>
<ForeName>Zhen-Ning</ForeName>
<Initials>ZN</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Key Laboratory of Systems Bioengineering , Ministry of Education , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>SynBio Research Platform , Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Qiao</LastName>
<ForeName>Jianjun</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Key Laboratory of Systems Bioengineering , Ministry of Education , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>SynBio Research Platform , Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhao</LastName>
<ForeName>Guang-Rong</ForeName>
<Initials>GR</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-6881-9042</Identifier>
<AffiliationInfo>
<Affiliation>Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Key Laboratory of Systems Bioengineering , Ministry of Education , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>SynBio Research Platform , Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300350 , China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D023362">Evaluation Study</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2018</Year>
<Month>12</Month>
<Day>11</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>J Agric Food Chem</MedlineTA>
<NlmUniqueID>0374755</NlmUniqueID>
<ISSNLinking>0021-8561</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>524-14-1</RegistryNumber>
<NameOfSubstance UI="D008316">Malonyl Coenzyme A</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 2.3.1.39</RegistryNumber>
<NameOfSubstance UI="D051080">Acyl-Carrier Protein S-Malonyltransferase</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>Q369O8926L</RegistryNumber>
<NameOfSubstance UI="D000077185">Resveratrol</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D051080" MajorTopicYN="N">Acyl-Carrier Protein S-Malonyltransferase</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D053898" MajorTopicYN="N">Biosynthetic Pathways</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D048230" MajorTopicYN="N">Corynebacterium glutamicum</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008316" MajorTopicYN="N">Malonyl Coenzyme A</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D060847" MajorTopicYN="N">Metabolic Engineering</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020075" MajorTopicYN="N">Phanerochaete</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000077185" MajorTopicYN="N">Resveratrol</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">Escherichia coli</Keyword>
<Keyword MajorTopicYN="N">combinatorial optimization</Keyword>
<Keyword MajorTopicYN="N">intracellular environment</Keyword>
<Keyword MajorTopicYN="N">metabolic engineering</Keyword>
<Keyword MajorTopicYN="N">resveratrol</Keyword>
<Keyword MajorTopicYN="N">synthetic biology</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="pubmed">
<Year>2018</Year>
<Month>11</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2019</Year>
<Month>4</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2018</Year>
<Month>11</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">30488696</ArticleId>
<ArticleId IdType="doi">10.1021/acs.jafc.8b05014</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name>
</noRegion>
<name sortKey="Liu, Zhen Ning" sort="Liu, Zhen Ning" uniqKey="Liu Z" first="Zhen-Ning" last="Liu">Zhen-Ning Liu</name>
<name sortKey="Liu, Zhen Ning" sort="Liu, Zhen Ning" uniqKey="Liu Z" first="Zhen-Ning" last="Liu">Zhen-Ning Liu</name>
<name sortKey="Liu, Zhen Ning" sort="Liu, Zhen Ning" uniqKey="Liu Z" first="Zhen-Ning" last="Liu">Zhen-Ning Liu</name>
<name sortKey="Qiao, Jianjun" sort="Qiao, Jianjun" uniqKey="Qiao J" first="Jianjun" last="Qiao">Jianjun Qiao</name>
<name sortKey="Qiao, Jianjun" sort="Qiao, Jianjun" uniqKey="Qiao J" first="Jianjun" last="Qiao">Jianjun Qiao</name>
<name sortKey="Qiao, Jianjun" sort="Qiao, Jianjun" uniqKey="Qiao J" first="Jianjun" last="Qiao">Jianjun Qiao</name>
<name sortKey="Wu, Bi Han" sort="Wu, Bi Han" uniqKey="Wu B" first="Bi-Han" last="Wu">Bi-Han Wu</name>
<name sortKey="Wu, Bi Han" sort="Wu, Bi Han" uniqKey="Wu B" first="Bi-Han" last="Wu">Bi-Han Wu</name>
<name sortKey="Wu, Bi Han" sort="Wu, Bi Han" uniqKey="Wu B" first="Bi-Han" last="Wu">Bi-Han Wu</name>
<name sortKey="Zhao, Guang Rong" sort="Zhao, Guang Rong" uniqKey="Zhao G" first="Guang-Rong" last="Zhao">Guang-Rong Zhao</name>
<name sortKey="Zhao, Guang Rong" sort="Zhao, Guang Rong" uniqKey="Zhao G" first="Guang-Rong" last="Zhao">Guang-Rong Zhao</name>
<name sortKey="Zhao, Guang Rong" sort="Zhao, Guang Rong" uniqKey="Zhao G" first="Guang-Rong" last="Zhao">Guang-Rong Zhao</name>
<name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name>
<name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name>
</country>
</tree>
</affiliations>
</record>

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