Stereospecificity in the enzymatic hydrolysis of cyclosarin (GF)
Enzymatic catalysis is one means of accelerating the rate of hydrolysis of G-type organophosphorus nerve agents. Here, the stereospecificity of the catalysis of cyclosarin (GF, O-cyclohexyl methylphosphonofluoridate) hydrolysis by several enzymes was investigated. Stereospecificity was not evident a...
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| Veröffentlicht in: | Enzyme and microbial technology 2005-10, Vol.37 (5), p.547-555 |
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| creator | Harvey, Steven P. Kolakowski, Jan E. Cheng, Tu-Chen Rastogi, Vipin K. Reiff, Louis P. DeFrank, Joseph J. Raushel, Frank M. Hill, Craig |
| description | Enzymatic catalysis is one means of accelerating the rate of hydrolysis of G-type organophosphorus nerve agents. Here, the stereospecificity of the catalysis of cyclosarin (GF,
O-cyclohexyl methylphosphonofluoridate) hydrolysis by several enzymes was investigated. Stereospecificity was not evident at 3
mM GF but was evident at 0.5
mM GF. The differential effect was apparently due to fluoride-catalyzed racemization of the substrate.
Alteromonas sp. JD6.5 organophosphorus acid anhydrolase (OPAA),
Alteromonas haloplanktis OPAA and the wild-type phosphotriesterase (PTE) enzymes were all found to catalyze preferentially the hydrolysis of the (+)GF isomer, as determined by GC analysis of the remaining unreacted (−)GF isomer. Acetylcholinesterase inhibition experiments showed the purified (−)GF isomer to be approximately twice as toxic as the racemic mixture. One PTE mutant, H254G/H259W/L303T, was found to reverse the native PTE stereospecificity and preferentially catalyze the hydrolysis of the (−)GF isomer, as shown by its complementation of
Alteromonas sp. JD6.5 OPAA and by GC analysis of the remaining (+)GF isomer. This procedure also permitted the individual preparation of either of the two GF isomers by enzymatic degradation followed by extraction of the remaining isomer. |
| doi_str_mv | 10.1016/j.enzmictec.2005.04.004 |
| format | Article |
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O-cyclohexyl methylphosphonofluoridate) hydrolysis by several enzymes was investigated. Stereospecificity was not evident at 3
mM GF but was evident at 0.5
mM GF. The differential effect was apparently due to fluoride-catalyzed racemization of the substrate.
Alteromonas sp. JD6.5 organophosphorus acid anhydrolase (OPAA),
Alteromonas haloplanktis OPAA and the wild-type phosphotriesterase (PTE) enzymes were all found to catalyze preferentially the hydrolysis of the (+)GF isomer, as determined by GC analysis of the remaining unreacted (−)GF isomer. Acetylcholinesterase inhibition experiments showed the purified (−)GF isomer to be approximately twice as toxic as the racemic mixture. One PTE mutant, H254G/H259W/L303T, was found to reverse the native PTE stereospecificity and preferentially catalyze the hydrolysis of the (−)GF isomer, as shown by its complementation of
Alteromonas sp. JD6.5 OPAA and by GC analysis of the remaining (+)GF isomer. This procedure also permitted the individual preparation of either of the two GF isomers by enzymatic degradation followed by extraction of the remaining isomer.</description><identifier>ISSN: 0141-0229</identifier><identifier>EISSN: 1879-0909</identifier><identifier>DOI: 10.1016/j.enzmictec.2005.04.004</identifier><identifier>CODEN: EMTED2</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Acetylcholinesterase ; Alteromonas haloplanktis ; Bioconversions. Hemisynthesis ; Biological and medical sciences ; Biotechnology ; Cyclosarin ; Enzyme ; Fundamental and applied biological sciences. Psychology ; Isomer ; Methods. Procedures. Technologies ; Stereochemistry ; Stereospecificity</subject><ispartof>Enzyme and microbial technology, 2005-10, Vol.37 (5), p.547-555</ispartof><rights>2005 Elsevier Inc.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-3865264a0105fe00d0d399caded2f6ae0cb0f3e7db74ea0ce6db39cefcbaf42e3</citedby><cites>FETCH-LOGICAL-c376t-3865264a0105fe00d0d399caded2f6ae0cb0f3e7db74ea0ce6db39cefcbaf42e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.enzmictec.2005.04.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17018634$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Harvey, Steven P.</creatorcontrib><creatorcontrib>Kolakowski, Jan E.</creatorcontrib><creatorcontrib>Cheng, Tu-Chen</creatorcontrib><creatorcontrib>Rastogi, Vipin K.</creatorcontrib><creatorcontrib>Reiff, Louis P.</creatorcontrib><creatorcontrib>DeFrank, Joseph J.</creatorcontrib><creatorcontrib>Raushel, Frank M.</creatorcontrib><creatorcontrib>Hill, Craig</creatorcontrib><title>Stereospecificity in the enzymatic hydrolysis of cyclosarin (GF)</title><title>Enzyme and microbial technology</title><description>Enzymatic catalysis is one means of accelerating the rate of hydrolysis of G-type organophosphorus nerve agents. Here, the stereospecificity of the catalysis of cyclosarin (GF,
O-cyclohexyl methylphosphonofluoridate) hydrolysis by several enzymes was investigated. Stereospecificity was not evident at 3
mM GF but was evident at 0.5
mM GF. The differential effect was apparently due to fluoride-catalyzed racemization of the substrate.
Alteromonas sp. JD6.5 organophosphorus acid anhydrolase (OPAA),
Alteromonas haloplanktis OPAA and the wild-type phosphotriesterase (PTE) enzymes were all found to catalyze preferentially the hydrolysis of the (+)GF isomer, as determined by GC analysis of the remaining unreacted (−)GF isomer. Acetylcholinesterase inhibition experiments showed the purified (−)GF isomer to be approximately twice as toxic as the racemic mixture. One PTE mutant, H254G/H259W/L303T, was found to reverse the native PTE stereospecificity and preferentially catalyze the hydrolysis of the (−)GF isomer, as shown by its complementation of
Alteromonas sp. JD6.5 OPAA and by GC analysis of the remaining (+)GF isomer. This procedure also permitted the individual preparation of either of the two GF isomers by enzymatic degradation followed by extraction of the remaining isomer.</description><subject>Acetylcholinesterase</subject><subject>Alteromonas haloplanktis</subject><subject>Bioconversions. Hemisynthesis</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cyclosarin</subject><subject>Enzyme</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Isomer</subject><subject>Methods. Procedures. Technologies</subject><subject>Stereochemistry</subject><subject>Stereospecificity</subject><issn>0141-0229</issn><issn>1879-0909</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkE1Lw0AQhhdRsFZ_g7koekicTbZJc7MUW4WCB_W8bGZn6ZZ81N2tEH-9KS169DQwPO87zMPYNYeEA88fNgm1343FQJikAJMERAIgTtiIT4syhhLKUzYCLngMaVqeswvvNwDDQsCIPb4FctT5LaE1Fm3oI9tGYU3R0No3KliM1r12Xd1766PORNhj3XnlBuxuubi_ZGdG1Z6ujnPMPhZP7_PnePW6fJnPVjFmRR7ibJpP0lwo4DAxBKBBZ2WJSpNOTa4IsAKTUaGrQpACpFxXWYlksFJGpJSN2e2hd-u6zx35IBvrkepatdTtvOSFKPIshQEsDiC6zntHRm6dbZTrJQe5NyY38teY3BuTIORgbEjeHE8oj6o2TrVo_V-8AD7Nsz03O3A0_PtlyUmPllokbR1hkLqz_976AUQFh1w</recordid><startdate>20051003</startdate><enddate>20051003</enddate><creator>Harvey, Steven P.</creator><creator>Kolakowski, Jan E.</creator><creator>Cheng, Tu-Chen</creator><creator>Rastogi, Vipin K.</creator><creator>Reiff, Louis P.</creator><creator>DeFrank, Joseph J.</creator><creator>Raushel, Frank M.</creator><creator>Hill, Craig</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20051003</creationdate><title>Stereospecificity in the enzymatic hydrolysis of cyclosarin (GF)</title><author>Harvey, Steven P. ; Kolakowski, Jan E. ; Cheng, Tu-Chen ; Rastogi, Vipin K. ; Reiff, Louis P. ; DeFrank, Joseph J. ; Raushel, Frank M. ; Hill, Craig</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-3865264a0105fe00d0d399caded2f6ae0cb0f3e7db74ea0ce6db39cefcbaf42e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetylcholinesterase</topic><topic>Alteromonas haloplanktis</topic><topic>Bioconversions. Hemisynthesis</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cyclosarin</topic><topic>Enzyme</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Isomer</topic><topic>Methods. Procedures. Technologies</topic><topic>Stereochemistry</topic><topic>Stereospecificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harvey, Steven P.</creatorcontrib><creatorcontrib>Kolakowski, Jan E.</creatorcontrib><creatorcontrib>Cheng, Tu-Chen</creatorcontrib><creatorcontrib>Rastogi, Vipin K.</creatorcontrib><creatorcontrib>Reiff, Louis P.</creatorcontrib><creatorcontrib>DeFrank, Joseph J.</creatorcontrib><creatorcontrib>Raushel, Frank M.</creatorcontrib><creatorcontrib>Hill, Craig</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Enzyme and microbial technology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harvey, Steven P.</au><au>Kolakowski, Jan E.</au><au>Cheng, Tu-Chen</au><au>Rastogi, Vipin K.</au><au>Reiff, Louis P.</au><au>DeFrank, Joseph J.</au><au>Raushel, Frank M.</au><au>Hill, Craig</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereospecificity in the enzymatic hydrolysis of cyclosarin (GF)</atitle><jtitle>Enzyme and microbial technology</jtitle><date>2005-10-03</date><risdate>2005</risdate><volume>37</volume><issue>5</issue><spage>547</spage><epage>555</epage><pages>547-555</pages><issn>0141-0229</issn><eissn>1879-0909</eissn><coden>EMTED2</coden><abstract>Enzymatic catalysis is one means of accelerating the rate of hydrolysis of G-type organophosphorus nerve agents. Here, the stereospecificity of the catalysis of cyclosarin (GF,
O-cyclohexyl methylphosphonofluoridate) hydrolysis by several enzymes was investigated. Stereospecificity was not evident at 3
mM GF but was evident at 0.5
mM GF. The differential effect was apparently due to fluoride-catalyzed racemization of the substrate.
Alteromonas sp. JD6.5 organophosphorus acid anhydrolase (OPAA),
Alteromonas haloplanktis OPAA and the wild-type phosphotriesterase (PTE) enzymes were all found to catalyze preferentially the hydrolysis of the (+)GF isomer, as determined by GC analysis of the remaining unreacted (−)GF isomer. Acetylcholinesterase inhibition experiments showed the purified (−)GF isomer to be approximately twice as toxic as the racemic mixture. One PTE mutant, H254G/H259W/L303T, was found to reverse the native PTE stereospecificity and preferentially catalyze the hydrolysis of the (−)GF isomer, as shown by its complementation of
Alteromonas sp. JD6.5 OPAA and by GC analysis of the remaining (+)GF isomer. This procedure also permitted the individual preparation of either of the two GF isomers by enzymatic degradation followed by extraction of the remaining isomer.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><doi>10.1016/j.enzmictec.2005.04.004</doi><tpages>9</tpages></addata></record> |
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| subjects | Acetylcholinesterase Alteromonas haloplanktis Bioconversions. Hemisynthesis Biological and medical sciences Biotechnology Cyclosarin Enzyme Fundamental and applied biological sciences. Psychology Isomer Methods. Procedures. Technologies Stereochemistry Stereospecificity |
| title | Stereospecificity in the enzymatic hydrolysis of cyclosarin (GF) |
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