Enhancing fatty acid production by the expression of the regulatory transcription factor FadR
Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid...
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| Veröffentlicht in: | Metabolic engineering 2012-11, Vol.14 (6), p.653-660 |
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| creator | Zhang, Fuzhong Ouellet, Mario Batth, Tanveer S. Adams, Paul D. Petzold, Christopher J. Mukhopadhyay, Aindrila Keasling, Jay D. |
| description | Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid titer by 7.5-fold over our previously engineered fatty acid-producing strain, reaching 5.2±0.5g/L and 73% of the theoretical yield. The mechanism by which FadR enhanced fatty acid yield was studied by whole-genome transcriptional analysis (microarray) and targeted proteomics. Overexpression of FadR led to transcriptional changes for many genes, including genes involved in fatty acid pathways. The biggest transcriptional changes in fatty acid pathway genes included fabB, fabF, and accA. Overexpression of any of these genes alone did not result in a high yield comparable to fadR expression, indicating that FadR enhanced fatty acid production globally by tuning the expression levels of many genes to optimal levels.
► FadR overexpression increased fatty acid yield by 7.5-fold under optimal condition. ► We produced 5.2g/L fatty acids, reaching 73% of theoretical yield. ► FadR expression leads to many transcriptional changes. ► Expression of single gene examined did not result in a high fatty acid yield. ► FadR enhanced fatty acid production by tuning the expression levels of many genes. |
| doi_str_mv | 10.1016/j.ymben.2012.08.009 |
| format | Article |
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► FadR overexpression increased fatty acid yield by 7.5-fold under optimal condition. ► We produced 5.2g/L fatty acids, reaching 73% of theoretical yield. ► FadR expression leads to many transcriptional changes. ► Expression of single gene examined did not result in a high fatty acid yield. ► FadR enhanced fatty acid production by tuning the expression levels of many genes.</description><identifier>ISSN: 1096-7176</identifier><identifier>EISSN: 1096-7184</identifier><identifier>DOI: 10.1016/j.ymben.2012.08.009</identifier><identifier>PMID: 23026122</identifier><language>eng</language><publisher>Belgium: Elsevier Inc</publisher><subject>3-Oxoacyl-(Acyl-Carrier-Protein) Synthase ; Acetyl-CoA Carboxylase ; Acetyltransferases ; Bacterial Proteins - physiology ; Biofuels ; DNA microarrays ; Escherichia coli ; Escherichia coli - physiology ; Escherichia coli Proteins ; FadR ; Fatty acid production ; Fatty Acid Synthase, Type II - genetics ; Fatty Acid Synthase, Type II - metabolism ; Fatty acids ; Fatty Acids - biosynthesis ; Fatty Acids - isolation & purification ; Gene Expression Regulation, Enzymologic - physiology ; Genetic Enhancement - methods ; Global regulation ; Metabolic engineering ; proteomics ; Regulatory Elements, Transcriptional - genetics ; Repressor Proteins - physiology ; Transcription factors</subject><ispartof>Metabolic engineering, 2012-11, Vol.14 (6), p.653-660</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-49547205ea9f57c4986bdc41cf3fd1b61d7511bb36814d77b7bc5d1cec1c687e3</citedby><cites>FETCH-LOGICAL-c485t-49547205ea9f57c4986bdc41cf3fd1b61d7511bb36814d77b7bc5d1cec1c687e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ymben.2012.08.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23026122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1153280$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Fuzhong</creatorcontrib><creatorcontrib>Ouellet, Mario</creatorcontrib><creatorcontrib>Batth, Tanveer S.</creatorcontrib><creatorcontrib>Adams, Paul D.</creatorcontrib><creatorcontrib>Petzold, Christopher J.</creatorcontrib><creatorcontrib>Mukhopadhyay, Aindrila</creatorcontrib><creatorcontrib>Keasling, Jay D.</creatorcontrib><creatorcontrib>Joint Bioenergy Institute (JBEI)</creatorcontrib><title>Enhancing fatty acid production by the expression of the regulatory transcription factor FadR</title><title>Metabolic engineering</title><addtitle>Metab Eng</addtitle><description>Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid titer by 7.5-fold over our previously engineered fatty acid-producing strain, reaching 5.2±0.5g/L and 73% of the theoretical yield. The mechanism by which FadR enhanced fatty acid yield was studied by whole-genome transcriptional analysis (microarray) and targeted proteomics. Overexpression of FadR led to transcriptional changes for many genes, including genes involved in fatty acid pathways. The biggest transcriptional changes in fatty acid pathway genes included fabB, fabF, and accA. Overexpression of any of these genes alone did not result in a high yield comparable to fadR expression, indicating that FadR enhanced fatty acid production globally by tuning the expression levels of many genes to optimal levels.
► FadR overexpression increased fatty acid yield by 7.5-fold under optimal condition. ► We produced 5.2g/L fatty acids, reaching 73% of theoretical yield. ► FadR expression leads to many transcriptional changes. ► Expression of single gene examined did not result in a high fatty acid yield. ► FadR enhanced fatty acid production by tuning the expression levels of many genes.</description><subject>3-Oxoacyl-(Acyl-Carrier-Protein) Synthase</subject><subject>Acetyl-CoA Carboxylase</subject><subject>Acetyltransferases</subject><subject>Bacterial Proteins - physiology</subject><subject>Biofuels</subject><subject>DNA microarrays</subject><subject>Escherichia coli</subject><subject>Escherichia coli - physiology</subject><subject>Escherichia coli Proteins</subject><subject>FadR</subject><subject>Fatty acid production</subject><subject>Fatty Acid Synthase, Type II - genetics</subject><subject>Fatty Acid Synthase, Type II - metabolism</subject><subject>Fatty acids</subject><subject>Fatty Acids - biosynthesis</subject><subject>Fatty Acids - isolation & purification</subject><subject>Gene Expression Regulation, Enzymologic - physiology</subject><subject>Genetic Enhancement - methods</subject><subject>Global regulation</subject><subject>Metabolic engineering</subject><subject>proteomics</subject><subject>Regulatory Elements, Transcriptional - genetics</subject><subject>Repressor Proteins - physiology</subject><subject>Transcription factors</subject><issn>1096-7176</issn><issn>1096-7184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-LFDEQxRtR3HX1EwjSePIybSr9J-mDB1l2V2FBED1KSCrVOxlmkjFJL8633_TMukc9VXj8XhUvr6reAmuAwfBx0xx2hnzDGfCGyYax8Vl1DmwcVgJk9_zpLYaz6lVKG8YA-hFeVme8ZXwAzs-rX1d-rT06f1dPOudDrdHZeh-DnTG74GtzqPOaavqzj5TSooTpqES6m7c6h1iAqH3C6PZHx6SxqPW1tt9fVy8mvU305nFeVD-vr35cflndfrv5evn5doWd7POqG_tOcNaTHqdeYDfKwVjsAKd2smAGsKIHMKYdJHRWCCMM9haQEHCQgtqL6v1pb0jZqYQuE64xeE-YVQndcskK9OEElXS_Z0pZ7VxC2m61pzAnBVxwASNn8v8o9CCYaLuxoO0JxRhSijSpfXQ7HQ8KmFp6Uht17EktPSkmVempuN49HpjNjuyT528xBfh0Aqh8272juKQij2RdXELZ4P554AECZ6Tn</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Zhang, Fuzhong</creator><creator>Ouellet, Mario</creator><creator>Batth, Tanveer S.</creator><creator>Adams, Paul D.</creator><creator>Petzold, Christopher J.</creator><creator>Mukhopadhyay, Aindrila</creator><creator>Keasling, Jay D.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>OTOTI</scope></search><sort><creationdate>201211</creationdate><title>Enhancing fatty acid production by the expression of the regulatory transcription factor FadR</title><author>Zhang, Fuzhong ; Ouellet, Mario ; Batth, Tanveer S. ; Adams, Paul D. ; Petzold, Christopher J. ; Mukhopadhyay, Aindrila ; Keasling, Jay D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-49547205ea9f57c4986bdc41cf3fd1b61d7511bb36814d77b7bc5d1cec1c687e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3-Oxoacyl-(Acyl-Carrier-Protein) Synthase</topic><topic>Acetyl-CoA Carboxylase</topic><topic>Acetyltransferases</topic><topic>Bacterial Proteins - physiology</topic><topic>Biofuels</topic><topic>DNA microarrays</topic><topic>Escherichia coli</topic><topic>Escherichia coli - physiology</topic><topic>Escherichia coli Proteins</topic><topic>FadR</topic><topic>Fatty acid production</topic><topic>Fatty Acid Synthase, Type II - genetics</topic><topic>Fatty Acid Synthase, Type II - metabolism</topic><topic>Fatty acids</topic><topic>Fatty Acids - biosynthesis</topic><topic>Fatty Acids - isolation & purification</topic><topic>Gene Expression Regulation, Enzymologic - physiology</topic><topic>Genetic Enhancement - methods</topic><topic>Global regulation</topic><topic>Metabolic engineering</topic><topic>proteomics</topic><topic>Regulatory Elements, Transcriptional - genetics</topic><topic>Repressor Proteins - physiology</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Fuzhong</creatorcontrib><creatorcontrib>Ouellet, Mario</creatorcontrib><creatorcontrib>Batth, Tanveer S.</creatorcontrib><creatorcontrib>Adams, Paul D.</creatorcontrib><creatorcontrib>Petzold, Christopher J.</creatorcontrib><creatorcontrib>Mukhopadhyay, Aindrila</creatorcontrib><creatorcontrib>Keasling, Jay D.</creatorcontrib><creatorcontrib>Joint Bioenergy Institute (JBEI)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Metabolic engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Fuzhong</au><au>Ouellet, Mario</au><au>Batth, Tanveer S.</au><au>Adams, Paul D.</au><au>Petzold, Christopher J.</au><au>Mukhopadhyay, Aindrila</au><au>Keasling, Jay D.</au><aucorp>Joint Bioenergy Institute (JBEI)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancing fatty acid production by the expression of the regulatory transcription factor FadR</atitle><jtitle>Metabolic engineering</jtitle><addtitle>Metab Eng</addtitle><date>2012-11</date><risdate>2012</risdate><volume>14</volume><issue>6</issue><spage>653</spage><epage>660</epage><pages>653-660</pages><issn>1096-7176</issn><eissn>1096-7184</eissn><abstract>Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid titer by 7.5-fold over our previously engineered fatty acid-producing strain, reaching 5.2±0.5g/L and 73% of the theoretical yield. The mechanism by which FadR enhanced fatty acid yield was studied by whole-genome transcriptional analysis (microarray) and targeted proteomics. Overexpression of FadR led to transcriptional changes for many genes, including genes involved in fatty acid pathways. The biggest transcriptional changes in fatty acid pathway genes included fabB, fabF, and accA. Overexpression of any of these genes alone did not result in a high yield comparable to fadR expression, indicating that FadR enhanced fatty acid production globally by tuning the expression levels of many genes to optimal levels.
► FadR overexpression increased fatty acid yield by 7.5-fold under optimal condition. ► We produced 5.2g/L fatty acids, reaching 73% of theoretical yield. ► FadR expression leads to many transcriptional changes. ► Expression of single gene examined did not result in a high fatty acid yield. ► FadR enhanced fatty acid production by tuning the expression levels of many genes.</abstract><cop>Belgium</cop><pub>Elsevier Inc</pub><pmid>23026122</pmid><doi>10.1016/j.ymben.2012.08.009</doi><tpages>8</tpages></addata></record> |
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| ispartof | Metabolic engineering, 2012-11, Vol.14 (6), p.653-660 |
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| subjects | 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase Acetyl-CoA Carboxylase Acetyltransferases Bacterial Proteins - physiology Biofuels DNA microarrays Escherichia coli Escherichia coli - physiology Escherichia coli Proteins FadR Fatty acid production Fatty Acid Synthase, Type II - genetics Fatty Acid Synthase, Type II - metabolism Fatty acids Fatty Acids - biosynthesis Fatty Acids - isolation & purification Gene Expression Regulation, Enzymologic - physiology Genetic Enhancement - methods Global regulation Metabolic engineering proteomics Regulatory Elements, Transcriptional - genetics Repressor Proteins - physiology Transcription factors |
| title | Enhancing fatty acid production by the expression of the regulatory transcription factor FadR |
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