Rational Engineering of the Nonheme Iron- and 2‑Oxoglutarate-Dependent Oxygenase SptF
The Fe- and 2-oxoglutarate-dependent oxygenase SptF is a promising powerful biocatalys with unusual catalytic versatility and promiscuity. The site-specific random substitution of N150, I63, and N65, which are involved in substrate interactions, generated three compounds that were not produced by th...
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Veröffentlicht in: | Organic letters 2022-03, Vol.24 (8), p.1737-1741 |
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creator | Mori, Takahiro Yu, Ziheng Tao, Hui Abe, Ikuro |
description | The Fe- and 2-oxoglutarate-dependent oxygenase SptF is a promising powerful biocatalys with unusual catalytic versatility and promiscuity. The site-specific random substitution of N150, I63, and N65, which are involved in substrate interactions, generated three compounds that were not produced by the SptF wild type. The substrate binding mode was dramatically altered by the introduction of only one or two substitutions. These results provide insights into the engineering of Fe- and 2-oxoglutarate-dependent oxygenases for chemoenzymatic syntheses of bioactive compounds. |
doi_str_mv | 10.1021/acs.orglett.2c00409 |
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The site-specific random substitution of N150, I63, and N65, which are involved in substrate interactions, generated three compounds that were not produced by the SptF wild type. The substrate binding mode was dramatically altered by the introduction of only one or two substitutions. These results provide insights into the engineering of Fe- and 2-oxoglutarate-dependent oxygenases for chemoenzymatic syntheses of bioactive compounds.</description><identifier>ISSN: 1523-7060</identifier><identifier>ISSN: 1523-7052</identifier><identifier>EISSN: 1523-7052</identifier><identifier>DOI: 10.1021/acs.orglett.2c00409</identifier><identifier>PMID: 35194997</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Iron - chemistry ; Iron - metabolism ; Ketoglutaric Acids - chemistry ; Ketoglutaric Acids - metabolism ; Molecular Structure ; Oxygenases - chemistry ; Oxygenases - metabolism ; Protein Engineering ; Substrate Specificity</subject><ispartof>Organic letters, 2022-03, Vol.24 (8), p.1737-1741</ispartof><rights>2022 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a411t-406da4d054fca1b90c89572b9f50d7b2601d00e86efe2ddc8d80b7378b7eb0103</citedby><cites>FETCH-LOGICAL-a411t-406da4d054fca1b90c89572b9f50d7b2601d00e86efe2ddc8d80b7378b7eb0103</cites><orcidid>0000-0002-2754-5858 ; 0000-0002-3640-888X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.orglett.2c00409$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.orglett.2c00409$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27081,27929,27930,56743,56793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35194997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mori, Takahiro</creatorcontrib><creatorcontrib>Yu, Ziheng</creatorcontrib><creatorcontrib>Tao, Hui</creatorcontrib><creatorcontrib>Abe, Ikuro</creatorcontrib><title>Rational Engineering of the Nonheme Iron- and 2‑Oxoglutarate-Dependent Oxygenase SptF</title><title>Organic letters</title><addtitle>Org. 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These results provide insights into the engineering of Fe- and 2-oxoglutarate-dependent oxygenases for chemoenzymatic syntheses of bioactive compounds.</description><subject>Iron - chemistry</subject><subject>Iron - metabolism</subject><subject>Ketoglutaric Acids - chemistry</subject><subject>Ketoglutaric Acids - metabolism</subject><subject>Molecular Structure</subject><subject>Oxygenases - chemistry</subject><subject>Oxygenases - metabolism</subject><subject>Protein Engineering</subject><subject>Substrate Specificity</subject><issn>1523-7060</issn><issn>1523-7052</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKAzEUhoMotlafQJAs3Ux7krkvpbZaKBa84HLITM5Mp0yTmmSg3fkKvqJP4pRWl67O4fD9_4GPkGsGQwacjURhh9pUDTo35AVAAOkJ6bOQ-14MIT_92yPokQtrVwCsu6TnpOeHLA3SNO6T92fhaq1EQyeqqhWiqVVFdUndEumTVktcI50ZrTwqlKT8-_NrsdVV0zphhEPvHjeoJCpHF9tdhUpYpC8bN70kZ6VoLF4d54C8TSev40dvvniYje_mnggYc14AkRSBhDAoC8HyFIokDWOep2UIMs55BEwCYBJhiVzKIpEJ5LEfJ3mMOTDwB-T20Lsx-qNF67J1bQtsGqFQtzbjkc9ZkAQ-61D_gBZGW2uwzDamXguzyxhke6NZZzQ7Gs2ORrvUzfFBm69R_mV-FXbA6ADs0yvdmk6m_bfyB6KThcw</recordid><startdate>20220304</startdate><enddate>20220304</enddate><creator>Mori, Takahiro</creator><creator>Yu, Ziheng</creator><creator>Tao, Hui</creator><creator>Abe, Ikuro</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0002-2754-5858</orcidid><orcidid>https://orcid.org/0000-0002-3640-888X</orcidid></search><sort><creationdate>20220304</creationdate><title>Rational Engineering of the Nonheme Iron- and 2‑Oxoglutarate-Dependent Oxygenase SptF</title><author>Mori, Takahiro ; Yu, Ziheng ; Tao, Hui ; Abe, Ikuro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a411t-406da4d054fca1b90c89572b9f50d7b2601d00e86efe2ddc8d80b7378b7eb0103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Iron - chemistry</topic><topic>Iron - metabolism</topic><topic>Ketoglutaric Acids - chemistry</topic><topic>Ketoglutaric Acids - metabolism</topic><topic>Molecular Structure</topic><topic>Oxygenases - chemistry</topic><topic>Oxygenases - metabolism</topic><topic>Protein Engineering</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mori, Takahiro</creatorcontrib><creatorcontrib>Yu, Ziheng</creatorcontrib><creatorcontrib>Tao, Hui</creatorcontrib><creatorcontrib>Abe, Ikuro</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><jtitle>Organic letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mori, Takahiro</au><au>Yu, Ziheng</au><au>Tao, Hui</au><au>Abe, Ikuro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rational Engineering of the Nonheme Iron- and 2‑Oxoglutarate-Dependent Oxygenase SptF</atitle><jtitle>Organic letters</jtitle><addtitle>Org. Lett</addtitle><date>2022-03-04</date><risdate>2022</risdate><volume>24</volume><issue>8</issue><spage>1737</spage><epage>1741</epage><pages>1737-1741</pages><issn>1523-7060</issn><issn>1523-7052</issn><eissn>1523-7052</eissn><abstract>The Fe- and 2-oxoglutarate-dependent oxygenase SptF is a promising powerful biocatalys with unusual catalytic versatility and promiscuity. The site-specific random substitution of N150, I63, and N65, which are involved in substrate interactions, generated three compounds that were not produced by the SptF wild type. The substrate binding mode was dramatically altered by the introduction of only one or two substitutions. 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subjects | Iron - chemistry Iron - metabolism Ketoglutaric Acids - chemistry Ketoglutaric Acids - metabolism Molecular Structure Oxygenases - chemistry Oxygenases - metabolism Protein Engineering Substrate Specificity |
title | Rational Engineering of the Nonheme Iron- and 2‑Oxoglutarate-Dependent Oxygenase SptF |
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