Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.
Identifieur interne : 001503 ( Main/Exploration ); précédent : 001502; suivant : 001504Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.
Auteurs : Lijin Duan [République populaire de Chine] ; Wentao Ding [République populaire de Chine] ; Xiaonan Liu [République populaire de Chine] ; Xiaozhi Cheng [République populaire de Chine] ; Jing Cai [République populaire de Chine] ; Erbing Hua [République populaire de Chine] ; Huifeng Jiang [République populaire de Chine]Source :
- Microbial cell factories [ 1475-2859 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
- biosynthèse : Kaempférols.
- génétique : Saccharomyces cerevisiae.
- métabolisme : Glucose, Saccharomyces cerevisiae.
- Fermentation, Génie métabolique, Voies de biosynthèse.
English descriptors
- KwdEn :
- MESH :
- chemical , biosynthesis : Kaempferols.
- chemical , metabolism : Glucose.
- genetics : Saccharomyces cerevisiae.
- metabolism : Saccharomyces cerevisiae.
- Biosynthetic Pathways, Fermentation, Metabolic Engineering.
Abstract
BACKGROUND
Kaempferol is a flavonol with broad bioactivity of anti-oxidant, anti-cancer, anti-diabetic, anti-microbial, cardio-protective and anti-asthma. Microbial synthesis of kaempferol is a promising strategy because of the low content in primary plant source.
METHODS
In this study, the biosynthesis pathway of kaempferol was constructed in the budding yeast Saccharomyces cerevisiae to produce kaempferol de novo, and several biological measures were taken for high production.
RESULTS
Firstly, a high efficient flavonol synthases (FLS) from Populus deltoides was introduced into the biosynthetic pathway of kaempferol. Secondly, a S. cerevisiae recombinant was constructed for de novo synthesis of kaempferol, which generated about 6.97 mg/L kaempferol from glucose. To further promote kaempferol production, the acetyl-CoA biosynthetic pathway was overexpressed and p-coumarate was supplied as substrate, which improved kaempferol titer by about 23 and 120%, respectively. Finally, a fed-batch process was developed for better kaempferol fermentation performance, and the production reached 66.29 mg/L in 40 h.
CONCLUSIONS
The titer of kaempferol in our engineered yeast is 2.5 times of the highest reported titer. Our study provides a possible strategy to produce kaempferol using microbial cell factory.
DOI: 10.1186/s12934-017-0774-x
PubMed: 28950867
PubMed Central: PMC5615808
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Ding, Wentao" sort="Ding, Wentao" uniqKey="Ding W" first="Wentao" last="Ding">Wentao Ding</name><affiliation wicri:level="3"><nlm:affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Liu, Xiaonan" sort="Liu, Xiaonan" uniqKey="Liu X" first="Xiaonan" last="Liu">Xiaonan Liu</name><affiliation wicri:level="3"><nlm:affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>University of Chinese Academy of Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Cheng, Xiaozhi" sort="Cheng, Xiaozhi" uniqKey="Cheng X" first="Xiaozhi" last="Cheng">Xiaozhi Cheng</name><affiliation wicri:level="3"><nlm:affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Cai, Jing" sort="Cai, Jing" uniqKey="Cai J" first="Jing" last="Cai">Jing Cai</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau</wicri:regionArea><wicri:noRegion>Macau</wicri:noRegion></affiliation></author><author><name sortKey="Hua, Erbing" sort="Hua, Erbing" uniqKey="Hua E" first="Erbing" last="Hua">Erbing Hua</name><affiliation wicri:level="3"><nlm:affiliation>Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China. huarb@tust.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author><author><name sortKey="Jiang, Huifeng" sort="Jiang, Huifeng" uniqKey="Jiang H" first="Huifeng" last="Jiang">Huifeng Jiang</name><affiliation wicri:level="3"><nlm:affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. jiang_hf@tib.cas.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin</wicri:regionArea><placeName><settlement type="city">Tianjin</settlement></placeName></affiliation></author></analytic><series><title level="j">Microbial cell factories</title><idno type="eISSN">1475-2859</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biosynthetic Pathways (MeSH)</term><term>Fermentation (MeSH)</term><term>Glucose (metabolism)</term><term>Kaempferols (biosynthesis)</term><term>Metabolic Engineering (MeSH)</term><term>Saccharomyces cerevisiae (genetics)</term><term>Saccharomyces cerevisiae (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Fermentation (MeSH)</term><term>Glucose (métabolisme)</term><term>Génie métabolique (MeSH)</term><term>Kaempférols (biosynthèse)</term><term>Saccharomyces cerevisiae (génétique)</term><term>Saccharomyces cerevisiae (métabolisme)</term><term>Voies de biosynthèse (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Kaempferols</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Kaempférols</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glucose</term><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Biosynthetic Pathways</term><term>Fermentation</term><term>Metabolic Engineering</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Fermentation</term><term>Génie métabolique</term><term>Voies de biosynthèse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Kaempferol is a flavonol with broad bioactivity of anti-oxidant, anti-cancer, anti-diabetic, anti-microbial, cardio-protective and anti-asthma. Microbial synthesis of kaempferol is a promising strategy because of the low content in primary plant source.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>In this study, the biosynthesis pathway of kaempferol was constructed in the budding yeast Saccharomyces cerevisiae to produce kaempferol de novo, and several biological measures were taken for high production.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Firstly, a high efficient flavonol synthases (FLS) from Populus deltoides was introduced into the biosynthetic pathway of kaempferol. Secondly, a S. cerevisiae recombinant was constructed for de novo synthesis of kaempferol, which generated about 6.97 mg/L kaempferol from glucose. To further promote kaempferol production, the acetyl-CoA biosynthetic pathway was overexpressed and p-coumarate was supplied as substrate, which improved kaempferol titer by about 23 and 120%, respectively. Finally, a fed-batch process was developed for better kaempferol fermentation performance, and the production reached 66.29 mg/L in 40 h.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>The titer of kaempferol in our engineered yeast is 2.5 times of the highest reported titer. Our study provides a possible strategy to produce kaempferol using microbial cell factory.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28950867</PMID><DateCompleted><Year>2018</Year><Month>05</Month><Day>14</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1475-2859</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Sep</Month><Day>26</Day></PubDate></JournalIssue><Title>Microbial cell factories</Title><ISOAbbreviation>Microb Cell Fact</ISOAbbreviation></Journal><ArticleTitle>Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.</ArticleTitle><Pagination><MedlinePgn>165</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1186/s12934-017-0774-x</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Kaempferol is a flavonol with broad bioactivity of anti-oxidant, anti-cancer, anti-diabetic, anti-microbial, cardio-protective and anti-asthma. Microbial synthesis of kaempferol is a promising strategy because of the low content in primary plant source.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In this study, the biosynthesis pathway of kaempferol was constructed in the budding yeast Saccharomyces cerevisiae to produce kaempferol de novo, and several biological measures were taken for high production.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Firstly, a high efficient flavonol synthases (FLS) from Populus deltoides was introduced into the biosynthetic pathway of kaempferol. Secondly, a S. cerevisiae recombinant was constructed for de novo synthesis of kaempferol, which generated about 6.97 mg/L kaempferol from glucose. To further promote kaempferol production, the acetyl-CoA biosynthetic pathway was overexpressed and p-coumarate was supplied as substrate, which improved kaempferol titer by about 23 and 120%, respectively. Finally, a fed-batch process was developed for better kaempferol fermentation performance, and the production reached 66.29 mg/L in 40 h.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The titer of kaempferol in our engineered yeast is 2.5 times of the highest reported titer. Our study provides a possible strategy to produce kaempferol using microbial cell factory.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Duan</LastName><ForeName>Lijin</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Wentao</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Xiaonan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Xiaozhi</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hua</LastName><ForeName>Erbing</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China. huarb@tust.edu.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Huifeng</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. jiang_hf@tib.cas.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>09</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Microb Cell Fact</MedlineTA><NlmUniqueID>101139812</NlmUniqueID><ISSNLinking>1475-2859</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D044949">Kaempferols</NameOfSubstance></Chemical><Chemical><RegistryNumber>731P2LE49E</RegistryNumber><NameOfSubstance UI="C006552">kaempferol</NameOfSubstance></Chemical><Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber><NameOfSubstance UI="D005947">Glucose</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D053898" MajorTopicYN="N">Biosynthetic Pathways</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005285" MajorTopicYN="N">Fermentation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005947" MajorTopicYN="N">Glucose</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D044949" MajorTopicYN="N">Kaempferols</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D060847" MajorTopicYN="N">Metabolic Engineering</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012441" MajorTopicYN="N">Saccharomyces cerevisiae</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Acetyl-CoA</Keyword><Keyword MajorTopicYN="N">Flavonol synthase</Keyword><Keyword MajorTopicYN="N">Kaempferol</Keyword><Keyword MajorTopicYN="N">Saccharomyces cerevisiae</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>06</Month><Day>01</Day></PubMedPubDate><PubMedPubDate 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uniqKey="Duan L" first="Lijin" last="Duan">Lijin Duan</name></noRegion><name sortKey="Cai, Jing" sort="Cai, Jing" uniqKey="Cai J" first="Jing" last="Cai">Jing Cai</name><name sortKey="Cheng, Xiaozhi" sort="Cheng, Xiaozhi" uniqKey="Cheng X" first="Xiaozhi" last="Cheng">Xiaozhi Cheng</name><name sortKey="Ding, Wentao" sort="Ding, Wentao" uniqKey="Ding W" first="Wentao" last="Ding">Wentao Ding</name><name sortKey="Duan, Lijin" sort="Duan, Lijin" uniqKey="Duan L" first="Lijin" last="Duan">Lijin Duan</name><name sortKey="Hua, Erbing" sort="Hua, Erbing" uniqKey="Hua E" first="Erbing" last="Hua">Erbing Hua</name><name sortKey="Jiang, Huifeng" sort="Jiang, Huifeng" uniqKey="Jiang H" first="Huifeng" last="Jiang">Huifeng Jiang</name><name sortKey="Liu, Xiaonan" sort="Liu, Xiaonan" uniqKey="Liu X" first="Xiaonan" last="Liu">Xiaonan Liu</name><name sortKey="Liu, Xiaonan" sort="Liu, Xiaonan" uniqKey="Liu X" first="Xiaonan" last="Liu">Xiaonan Liu</name></country></tree></affiliations></record>Pour 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