Computing complex metabolic intervention strategies using constrained minimal cut sets
The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set o...
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Veröffentlicht in: | Metabolic engineering 2011-03, Vol.13 (2), p.204-213 |
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description | The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set of
target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to
Constrained MCSs (cMCSs) allowing for the additional definition of a set of
desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by
Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis. |
doi_str_mv | 10.1016/j.ymben.2010.12.004 |
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target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to
Constrained MCSs (cMCSs) allowing for the additional definition of a set of
desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by
Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis.</description><identifier>ISSN: 1096-7176</identifier><identifier>EISSN: 1096-7184</identifier><identifier>DOI: 10.1016/j.ymben.2010.12.004</identifier><identifier>PMID: 21147248</identifier><language>eng</language><publisher>Belgium: Elsevier Inc</publisher><subject>Algorithms ; Computer Simulation ; Elementary modes ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Ethanol - metabolism ; Ethanol production ; Gene Deletion ; Gene Knockout Techniques ; Genetic Engineering ; Metabolic engineering ; Metabolic Networks and Pathways - genetics ; Minimal cut sets ; Models, Biological ; Strain optimization ; Targeted modification</subject><ispartof>Metabolic engineering, 2011-03, Vol.13 (2), p.204-213</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright © 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-f2e912d259184748ea4126c8369aeb3a30a1c4c4398b4d305d3732eb74d699663</citedby><cites>FETCH-LOGICAL-c480t-f2e912d259184748ea4126c8369aeb3a30a1c4c4398b4d305d3732eb74d699663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1096717610001084$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21147248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hädicke, Oliver</creatorcontrib><creatorcontrib>Klamt, Steffen</creatorcontrib><title>Computing complex metabolic intervention strategies using constrained minimal cut sets</title><title>Metabolic engineering</title><addtitle>Metab Eng</addtitle><description>The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set of
target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to
Constrained MCSs (cMCSs) allowing for the additional definition of a set of
desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by
Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis.</description><subject>Algorithms</subject><subject>Computer Simulation</subject><subject>Elementary modes</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>Ethanol - metabolism</subject><subject>Ethanol production</subject><subject>Gene Deletion</subject><subject>Gene Knockout Techniques</subject><subject>Genetic Engineering</subject><subject>Metabolic engineering</subject><subject>Metabolic Networks and Pathways - genetics</subject><subject>Minimal cut sets</subject><subject>Models, Biological</subject><subject>Strain optimization</subject><subject>Targeted modification</subject><issn>1096-7176</issn><issn>1096-7184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1PwzAQhi0EolD4BUiQjanFX3HigQFVfElIDFBWy3GulavEKbZTwb_HJYURJp9Oz726e4zQGcFTgom4Wk0_2wrclOJth04x5nvoiGApJgUp-f5vXYgROg5hhTEhuSSHaEQJ4QXl5RF6m3Xtuo_WLTOTqgY-shairrrGmsy6CH4DLtrOZSF6HWFpIWR9GHi37VkHddZaZ1vdZKaPWYAYTtDBQjcBTnfvGM3vbl9nD5On5_vH2c3TxPASx8mCgiS0pmmrkhe8BM0JFaZkQmqomGZYE8MNZ7KseM1wXrOCUagKXgsphWBjdDnkrn333kOIqrXBQNNoB10flMy5yKks6L9kmecSsxzzRLKBNL4LwcNCrX06zn8qgtXWvFqpb_Nqa14RqvD31Pkuv69aqH9nflQn4GIAFrpTeultUPOXlCDStxQCM5KI64GAZGxjwatgLDgDtfVgoqo7--cKX3frnvo</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Hädicke, Oliver</creator><creator>Klamt, Steffen</creator><general>Elsevier Inc</general><scope>FBQ</scope><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></search><sort><creationdate>20110301</creationdate><title>Computing complex metabolic intervention strategies using constrained minimal cut sets</title><author>Hädicke, Oliver ; Klamt, Steffen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-f2e912d259184748ea4126c8369aeb3a30a1c4c4398b4d305d3732eb74d699663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Algorithms</topic><topic>Computer Simulation</topic><topic>Elementary modes</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>Ethanol - metabolism</topic><topic>Ethanol production</topic><topic>Gene Deletion</topic><topic>Gene Knockout Techniques</topic><topic>Genetic Engineering</topic><topic>Metabolic engineering</topic><topic>Metabolic Networks and Pathways - genetics</topic><topic>Minimal cut sets</topic><topic>Models, Biological</topic><topic>Strain optimization</topic><topic>Targeted modification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hädicke, Oliver</creatorcontrib><creatorcontrib>Klamt, Steffen</creatorcontrib><collection>AGRIS</collection><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><jtitle>Metabolic engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hädicke, Oliver</au><au>Klamt, Steffen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Computing complex metabolic intervention strategies using constrained minimal cut sets</atitle><jtitle>Metabolic engineering</jtitle><addtitle>Metab Eng</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>13</volume><issue>2</issue><spage>204</spage><epage>213</epage><pages>204-213</pages><issn>1096-7176</issn><eissn>1096-7184</eissn><abstract>The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set of
target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to
Constrained MCSs (cMCSs) allowing for the additional definition of a set of
desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by
Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis.</abstract><cop>Belgium</cop><pub>Elsevier Inc</pub><pmid>21147248</pmid><doi>10.1016/j.ymben.2010.12.004</doi><tpages>10</tpages></addata></record> |
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subjects | Algorithms Computer Simulation Elementary modes Escherichia coli Escherichia coli - genetics Escherichia coli - metabolism Ethanol - metabolism Ethanol production Gene Deletion Gene Knockout Techniques Genetic Engineering Metabolic engineering Metabolic Networks and Pathways - genetics Minimal cut sets Models, Biological Strain optimization Targeted modification |
title | Computing complex metabolic intervention strategies using constrained minimal cut sets |
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