Engineering and manipulation of a mevalonate pathway in Escherichia coli for isoprene production.
Identifieur interne : 000986 ( Main/Exploration ); précédent : 000985; suivant : 000987Engineering and manipulation of a mevalonate pathway in Escherichia coli for isoprene production.
Auteurs : Chun-Li Liu [République populaire de Chine] ; Hao-Ran Bi [République populaire de Chine] ; Zhonghu Bai [République populaire de Chine] ; Li-Hai Fan [République populaire de Chine] ; Tian-Wei Tan [République populaire de Chine]Source :
- Applied microbiology and biotechnology [ 1432-0614 ] ; 2019.
Descripteurs français
- KwdFr :
- Acide mévalonique (métabolisme), Alkyl et aryl transferases (génétique), Alkyl et aryl transferases (métabolisme), Butadiènes (MeSH), Carboxy-lyases (génétique), Carboxy-lyases (métabolisme), Composés organiques du phosphore (MeSH), Enterococcus faecalis (génétique), Escherichia coli (génétique), Escherichia coli (métabolisme), Fermentation (MeSH), Génie métabolique (méthodes), Hémiterpènes (biosynthèse), Hémiterpènes (génétique), Micro-organismes génétiquement modifiés (MeSH), Microbiologie industrielle (méthodes), Populus (génétique), Protéines recombinantes (génétique), Protéines recombinantes (métabolisme), Régulation de l'expression des gènes bactériens (MeSH).
- MESH :
- biosynthèse : Hémiterpènes.
- génétique : Alkyl et aryl transferases, Carboxy-lyases, Enterococcus faecalis, Escherichia coli, Hémiterpènes, Populus, Protéines recombinantes.
- métabolisme : Acide mévalonique, Alkyl et aryl transferases, Carboxy-lyases, Escherichia coli, Protéines recombinantes.
- méthodes : Génie métabolique, Microbiologie industrielle.
- Butadiènes, Composés organiques du phosphore, Fermentation, Micro-organismes génétiquement modifiés, Régulation de l'expression des gènes bactériens.
English descriptors
- KwdEn :
- Alkyl and Aryl Transferases (genetics), Alkyl and Aryl Transferases (metabolism), Butadienes (MeSH), Carboxy-Lyases (genetics), Carboxy-Lyases (metabolism), Enterococcus faecalis (genetics), Escherichia coli (genetics), Escherichia coli (metabolism), Fermentation (MeSH), Gene Expression Regulation, Bacterial (MeSH), Hemiterpenes (biosynthesis), Hemiterpenes (genetics), Industrial Microbiology (methods), Metabolic Engineering (methods), Mevalonic Acid (metabolism), Microorganisms, Genetically-Modified (MeSH), Organophosphorus Compounds (MeSH), Populus (genetics), Recombinant Proteins (genetics), Recombinant Proteins (metabolism).
- MESH :
- chemical , biosynthesis : Hemiterpenes.
- chemical , genetics : Alkyl and Aryl Transferases, Carboxy-Lyases, Hemiterpenes, Recombinant Proteins.
- chemical , metabolism : Alkyl and Aryl Transferases, Carboxy-Lyases, Mevalonic Acid, Recombinant Proteins.
- chemical : Butadienes, Organophosphorus Compounds.
- genetics : Enterococcus faecalis, Escherichia coli, Populus.
- metabolism : Escherichia coli.
- methods : Industrial Microbiology, Metabolic Engineering.
- Fermentation, Gene Expression Regulation, Bacterial, Microorganisms, Genetically-Modified.
Abstract
Isoprene is a useful phytochemical with high commercial values in many industrial applications including synthetic rubber, elastomers, isoprenoid medicines, and fossil fuel. Currently, isoprene is on large scale produced from petrochemical sources. An efficient biological process for isoprene production utilizing renewable feedstocks would be an important direction of research due to the fossil raw material depletion and air pollution. In this study, we introduced the mevalonate (MVA) pathway genes/acetoacetyl-coenzyme A thiolase (mvaE) and MVA synthase (mvaS) from Enterococcus faecalis (E. faecalis); MVA kinase (mvk) derived from Methanosarcina mazei (M. mazei); and phosphomevalonate kinase (pmk), diphosphomevalonate decarboxylase (mvaD), and isopentenyl diphosphate isomerase (idi) from Streptococcus pneumoniae (S. pneumoniae) to accelerate dimethylallyl diphosphate (DMAPP) accumulation in Escherichia coli (E. coli). Together with a codon-optimized isoprene synthase (ispS) from Populus alba (P. alba), E. coli strain succeeded in formation of isoprene. We then manipulated the heterologous MVA pathway for high-level production of isoprene, by controlling the gene expression levels of the MVA pathway genes. We engineered four E. coli strains which showed different gene expression levels and different isoprene productivities, and we also characterized them with quantitative real-time PCR and metabolite analysis. To further improve the isoprene titers and release the toxicity to cells, we developed the extraction fermentation by adding dodecane in cultures. Finally, strain BL2T7P1TrcP harboring balanced gene expression system produced 587 ± 47 mg/L isoprene, with a 5.2-fold titer improvement in comparison with strain BL7CT7P. This work indicated that a balanced metabolic flux played a significant role to improve the isoprene production via MVA pathway.
DOI: 10.1007/s00253-018-9472-9
PubMed: 30374674
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Binhu District Lihu Road no. 1800, Wuxi City, 214122, Jiangsu Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Binhu District Lihu Road no. 1800, Wuxi City, 214122, Jiangsu Province</wicri:regionArea><wicri:noRegion>Jiangsu Province</wicri:noRegion></affiliation></author><author><name sortKey="Bi, Hao Ran" sort="Bi, Hao Ran" uniqKey="Bi H" first="Hao-Ran" last="Bi">Hao-Ran Bi</name><affiliation wicri:level="3"><nlm:affiliation>National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Chaoyang District North Sanhuan Road no. 15, 100029, Beijing, People's Republic of 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xml:lang="en"><term>Alkyl and Aryl Transferases (genetics)</term><term>Alkyl and Aryl Transferases (metabolism)</term><term>Butadienes (MeSH)</term><term>Carboxy-Lyases (genetics)</term><term>Carboxy-Lyases (metabolism)</term><term>Enterococcus faecalis (genetics)</term><term>Escherichia coli (genetics)</term><term>Escherichia coli (metabolism)</term><term>Fermentation (MeSH)</term><term>Gene Expression Regulation, Bacterial (MeSH)</term><term>Hemiterpenes (biosynthesis)</term><term>Hemiterpenes (genetics)</term><term>Industrial Microbiology (methods)</term><term>Metabolic Engineering (methods)</term><term>Mevalonic Acid (metabolism)</term><term>Microorganisms, Genetically-Modified (MeSH)</term><term>Organophosphorus Compounds (MeSH)</term><term>Populus (genetics)</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide mévalonique (métabolisme)</term><term>Alkyl et aryl transferases (génétique)</term><term>Alkyl et aryl transferases (métabolisme)</term><term>Butadiènes (MeSH)</term><term>Carboxy-lyases (génétique)</term><term>Carboxy-lyases (métabolisme)</term><term>Composés organiques du phosphore (MeSH)</term><term>Enterococcus faecalis (génétique)</term><term>Escherichia coli (génétique)</term><term>Escherichia coli (métabolisme)</term><term>Fermentation (MeSH)</term><term>Génie métabolique (méthodes)</term><term>Hémiterpènes (biosynthèse)</term><term>Hémiterpènes (génétique)</term><term>Micro-organismes génétiquement modifiés (MeSH)</term><term>Microbiologie industrielle (méthodes)</term><term>Populus (génétique)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (métabolisme)</term><term>Régulation de l'expression des gènes bactériens (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Hemiterpenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Alkyl and Aryl Transferases</term><term>Carboxy-Lyases</term><term>Hemiterpenes</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Alkyl and Aryl Transferases</term><term>Carboxy-Lyases</term><term>Mevalonic Acid</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Butadienes</term><term>Organophosphorus Compounds</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Hémiterpènes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Enterococcus faecalis</term><term>Escherichia coli</term><term>Populus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Alkyl et aryl transferases</term><term>Carboxy-lyases</term><term>Enterococcus faecalis</term><term>Escherichia coli</term><term>Hémiterpènes</term><term>Populus</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Industrial Microbiology</term><term>Metabolic Engineering</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acide mévalonique</term><term>Alkyl et aryl transferases</term><term>Carboxy-lyases</term><term>Escherichia coli</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Génie métabolique</term><term>Microbiologie industrielle</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Fermentation</term><term>Gene Expression Regulation, Bacterial</term><term>Microorganisms, Genetically-Modified</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Butadiènes</term><term>Composés organiques du phosphore</term><term>Fermentation</term><term>Micro-organismes génétiquement modifiés</term><term>Régulation de l'expression des gènes bactériens</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Isoprene is a useful phytochemical with high commercial values in many industrial applications including synthetic rubber, elastomers, isoprenoid medicines, and fossil fuel. Currently, isoprene is on large scale produced from petrochemical sources. An efficient biological process for isoprene production utilizing renewable feedstocks would be an important direction of research due to the fossil raw material depletion and air pollution. In this study, we introduced the mevalonate (MVA) pathway genes/acetoacetyl-coenzyme A thiolase (mvaE) and MVA synthase (mvaS) from Enterococcus faecalis (E. faecalis); MVA kinase (mvk) derived from Methanosarcina mazei (M. mazei); and phosphomevalonate kinase (pmk), diphosphomevalonate decarboxylase (mvaD), and isopentenyl diphosphate isomerase (idi) from Streptococcus pneumoniae (S. pneumoniae) to accelerate dimethylallyl diphosphate (DMAPP) accumulation in Escherichia coli (E. coli). Together with a codon-optimized isoprene synthase (ispS) from Populus alba (P. alba), E. coli strain succeeded in formation of isoprene. We then manipulated the heterologous MVA pathway for high-level production of isoprene, by controlling the gene expression levels of the MVA pathway genes. We engineered four E. coli strains which showed different gene expression levels and different isoprene productivities, and we also characterized them with quantitative real-time PCR and metabolite analysis. To further improve the isoprene titers and release the toxicity to cells, we developed the extraction fermentation by adding dodecane in cultures. Finally, strain BL2T7P1TrcP harboring balanced gene expression system produced 587 ± 47 mg/L isoprene, with a 5.2-fold titer improvement in comparison with strain BL7CT7P. This work indicated that a balanced metabolic flux played a significant role to improve the isoprene production via MVA pathway.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30374674</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>13</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-0614</ISSN><JournalIssue CitedMedium="Internet"><Volume>103</Volume><Issue>1</Issue><PubDate><Year>2019</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Applied microbiology and biotechnology</Title><ISOAbbreviation>Appl Microbiol Biotechnol</ISOAbbreviation></Journal><ArticleTitle>Engineering and manipulation of a mevalonate pathway in Escherichia coli for isoprene production.</ArticleTitle><Pagination><MedlinePgn>239-250</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00253-018-9472-9</ELocationID><Abstract><AbstractText>Isoprene is a useful phytochemical with high commercial values in many industrial applications including synthetic rubber, elastomers, isoprenoid medicines, and fossil fuel. Currently, isoprene is on large scale produced from petrochemical sources. An efficient biological process for isoprene production utilizing renewable feedstocks would be an important direction of research due to the fossil raw material depletion and air pollution. In this study, we introduced the mevalonate (MVA) pathway genes/acetoacetyl-coenzyme A thiolase (mvaE) and MVA synthase (mvaS) from Enterococcus faecalis (E. faecalis); MVA kinase (mvk) derived from Methanosarcina mazei (M. mazei); and phosphomevalonate kinase (pmk), diphosphomevalonate decarboxylase (mvaD), and isopentenyl diphosphate isomerase (idi) from Streptococcus pneumoniae (S. pneumoniae) to accelerate dimethylallyl diphosphate (DMAPP) accumulation in Escherichia coli (E. coli). Together with a codon-optimized isoprene synthase (ispS) from Populus alba (P. alba), E. coli strain succeeded in formation of isoprene. We then manipulated the heterologous MVA pathway for high-level production of isoprene, by controlling the gene expression levels of the MVA pathway genes. We engineered four E. coli strains which showed different gene expression levels and different isoprene productivities, and we also characterized them with quantitative real-time PCR and metabolite analysis. To further improve the isoprene titers and release the toxicity to cells, we developed the extraction fermentation by adding dodecane in cultures. Finally, strain BL2T7P1TrcP harboring balanced gene expression system produced 587 ± 47 mg/L isoprene, with a 5.2-fold titer improvement in comparison with strain BL7CT7P. This work indicated that a balanced metabolic flux played a significant role to improve the isoprene production via MVA pathway.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Chun-Li</ForeName><Initials>CL</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-3107-1843</Identifier><AffiliationInfo><Affiliation>National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Chaoyang District North Sanhuan Road no. 15, 100029, Beijing, People's Republic of China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Binhu District Lihu Road no. 1800, Wuxi City, 214122, Jiangsu Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bi</LastName><ForeName>Hao-Ran</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Chaoyang District North Sanhuan Road no. 15, 100029, Beijing, People's Republic of China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bai</LastName><ForeName>Zhonghu</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Binhu District Lihu Road no. 1800, Wuxi City, 214122, Jiangsu Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Li-Hai</ForeName><Initials>LH</Initials><AffiliationInfo><Affiliation>National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Chaoyang District North Sanhuan Road no. 15, 100029, Beijing, People's Republic of China. fanlh@mail.buct.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Tian-Wei</ForeName><Initials>TW</Initials><AffiliationInfo><Affiliation>National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Chaoyang District North Sanhuan Road no. 15, 100029, Beijing, People's Republic of China. twtan@mail.buct.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>2013CB733600</GrantID><Agency>National Basic Research Program of China (973 program)</Agency><Country></Country></Grant><Grant><GrantID>21390202, 21476017</GrantID><Agency>National Nature Science Foundation of China</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>10</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Appl Microbiol Biotechnol</MedlineTA><NlmUniqueID>8406612</NlmUniqueID><ISSNLinking>0175-7598</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002070">Butadienes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D045782">Hemiterpenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009943">Organophosphorus Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0A62964IBU</RegistryNumber><NameOfSubstance UI="C005059">isoprene</NameOfSubstance></Chemical><Chemical><RegistryNumber>358-72-5</RegistryNumber><NameOfSubstance UI="C043060">3,3-dimethylallyl pyrophosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.5.-</RegistryNumber><NameOfSubstance UI="D019883">Alkyl and Aryl Transferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.5.1.-</RegistryNumber><NameOfSubstance UI="C093854">isoprene synthase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 4.1.1.-</RegistryNumber><NameOfSubstance UI="D002262">Carboxy-Lyases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 4.1.1.33</RegistryNumber><NameOfSubstance UI="C022503">pyrophosphomevalonate decarboxylase</NameOfSubstance></Chemical><Chemical><RegistryNumber>S5UOB36OCZ</RegistryNumber><NameOfSubstance UI="D008798">Mevalonic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D019883" MajorTopicYN="N">Alkyl and Aryl Transferases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002070" MajorTopicYN="N">Butadienes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002262" MajorTopicYN="N">Carboxy-Lyases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013293" MajorTopicYN="N">Enterococcus faecalis</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005285" MajorTopicYN="N">Fermentation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015964" MajorTopicYN="N">Gene Expression Regulation, Bacterial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045782" MajorTopicYN="N">Hemiterpenes</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007218" MajorTopicYN="N">Industrial Microbiology</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D060847" MajorTopicYN="N">Metabolic Engineering</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008798" MajorTopicYN="N">Mevalonic Acid</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000074041" MajorTopicYN="N">Microorganisms, Genetically-Modified</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009943" MajorTopicYN="N">Organophosphorus Compounds</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D032107" MajorTopicYN="N">Populus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Balanced gene expression</Keyword><Keyword MajorTopicYN="N">Escherichia coli</Keyword><Keyword MajorTopicYN="N">Isoprene</Keyword><Keyword MajorTopicYN="N">Mevalonate pathway</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>06</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>10</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>09</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>10</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>5</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>10</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30374674</ArticleId><ArticleId IdType="doi">10.1007/s00253-018-9472-9</ArticleId><ArticleId IdType="pii">10.1007/s00253-018-9472-9</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Liu, Chun Li" sort="Liu, Chun Li" uniqKey="Liu C" first="Chun-Li" last="Liu">Chun-Li Liu</name></noRegion><name sortKey="Bai, Zhonghu" sort="Bai, Zhonghu" uniqKey="Bai Z" first="Zhonghu" last="Bai">Zhonghu Bai</name><name sortKey="Bi, Hao Ran" sort="Bi, Hao Ran" uniqKey="Bi H" first="Hao-Ran" last="Bi">Hao-Ran Bi</name><name sortKey="Fan, Li Hai" sort="Fan, Li Hai" uniqKey="Fan L" first="Li-Hai" last="Fan">Li-Hai Fan</name><name sortKey="Liu, Chun Li" sort="Liu, Chun Li" uniqKey="Liu C" first="Chun-Li" last="Liu">Chun-Li Liu</name><name sortKey="Tan, Tian Wei" sort="Tan, Tian Wei" uniqKey="Tan T" first="Tian-Wei" last="Tan">Tian-Wei Tan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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