Influence of mutation in the regulatory domain of α-isopropylmalate synthase from Saccharomyces cerevisiae on its activity and feedback inhibition
Isoamyl alcohol (i-AmOH) is produced from α-ketoisocaproate in the l-leucine biosynthetic pathway in yeast and controlled by the negative feedback regulation of α-isopropylmalate synthase (IPMS), which senses the accumulation of l-leucine. It is known that i-AmOH production increases when mutations...
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| Veröffentlicht in: | Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2022-05, Vol.86 (6), p.755-762 |
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| creator | Takagi, Hironobu Yamamoto, Kazuki Matsuo, Yoshifumi Furuie, Miki Kasayuki, Yasuha Ohtani, Rina Shiotani, Mizuki Hasegawa, Tetsuya Ohnishi, Toru Ohashi, Masataka Johzuka, Katsuki Kurata, Atsushi Uegaki, Koichi |
| description | Isoamyl alcohol (i-AmOH) is produced from α-ketoisocaproate in the l-leucine biosynthetic pathway in yeast and controlled by the negative feedback regulation of α-isopropylmalate synthase (IPMS), which senses the accumulation of l-leucine. It is known that i-AmOH production increases when mutations in the regulatory domain reduce the susceptibility to feedback inhibition. However, the impact of mutations in this domain on the IPMS activity has not been examined. In this study, we obtained 5 IPMS mutants, encoding the LEU4 gene, N515D/S520P/S542F/A551D/A551V, that are tolerant to 5,5,5-trifluoro-dl-leucine. All mutant proteins were purified and examined for both IPMS activity and negative feedback activity by in vitro experiments. The results showed that not only the negative-feedback regulation by l-leucine was almost lost in all mutants, but also the IPMS activity was greatly decreased and the difference in IPMS activity among Leu4 mutants in the presence of l-leucine was significantly correlated with i-AmOH production. |
| doi_str_mv | 10.1093/bbb/zbac045 |
| format | Article |
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It is known that i-AmOH production increases when mutations in the regulatory domain reduce the susceptibility to feedback inhibition. However, the impact of mutations in this domain on the IPMS activity has not been examined. In this study, we obtained 5 IPMS mutants, encoding the LEU4 gene, N515D/S520P/S542F/A551D/A551V, that are tolerant to 5,5,5-trifluoro-dl-leucine. All mutant proteins were purified and examined for both IPMS activity and negative feedback activity by in vitro experiments. The results showed that not only the negative-feedback regulation by l-leucine was almost lost in all mutants, but also the IPMS activity was greatly decreased and the difference in IPMS activity among Leu4 mutants in the presence of l-leucine was significantly correlated with i-AmOH production.</description><identifier>ISSN: 1347-6947</identifier><identifier>EISSN: 1347-6947</identifier><identifier>DOI: 10.1093/bbb/zbac045</identifier><identifier>PMID: 35333283</identifier><language>eng</language><publisher>England</publisher><ispartof>Bioscience, biotechnology, and biochemistry, 2022-05, Vol.86 (6), p.755-762</ispartof><rights>The Author(s) 2022. 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It is known that i-AmOH production increases when mutations in the regulatory domain reduce the susceptibility to feedback inhibition. However, the impact of mutations in this domain on the IPMS activity has not been examined. In this study, we obtained 5 IPMS mutants, encoding the LEU4 gene, N515D/S520P/S542F/A551D/A551V, that are tolerant to 5,5,5-trifluoro-dl-leucine. All mutant proteins were purified and examined for both IPMS activity and negative feedback activity by in vitro experiments. The results showed that not only the negative-feedback regulation by l-leucine was almost lost in all mutants, but also the IPMS activity was greatly decreased and the difference in IPMS activity among Leu4 mutants in the presence of l-leucine was significantly correlated with i-AmOH production.</description><issn>1347-6947</issn><issn>1347-6947</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpNkc1KxTAQhYMo_q_cS5aCVJMm7W2XIv6B4EJdl0k68Ubb5pqkF-pr-CS-iM9kxKu4mmHycc5kDiEHnJ1wVotTpdTpmwLNZLFGtrmQs6ys5Wz9X79FdkJ4ZozVvOCbZEsUQoi8Etvk_WYw3YiDRuoM7ccI0bqB2oHGOVKPT2MH0fmJtq6HNE3Q50dmg1t4t5i6HtIz0jANcQ4BqfGup_eg9RxSN2kMVKPHpQ0WkkMSjoGCjnZp40RhaKlBbNPyL8lybpX9dt8jGwa6gPurukseLy8ezq-z27urm_Oz20znVR2zCqAtVaGBY5VXlShR1MYUvG1rqWRbFYyVNQOhBcsLAcCMgQQrnNVMItdilxz96Ka_vI4YYtPboLHrYEA3hiYvpWTpxLJK6PEPqr0LwaNpFt724KeGs-Y7hSal0KxSSPThSnhUPbZ_7O_ZxRckV4kV</recordid><startdate>20220524</startdate><enddate>20220524</enddate><creator>Takagi, Hironobu</creator><creator>Yamamoto, Kazuki</creator><creator>Matsuo, Yoshifumi</creator><creator>Furuie, Miki</creator><creator>Kasayuki, Yasuha</creator><creator>Ohtani, Rina</creator><creator>Shiotani, Mizuki</creator><creator>Hasegawa, Tetsuya</creator><creator>Ohnishi, Toru</creator><creator>Ohashi, Masataka</creator><creator>Johzuka, Katsuki</creator><creator>Kurata, Atsushi</creator><creator>Uegaki, Koichi</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6659-2596</orcidid><orcidid>https://orcid.org/0000-0002-0235-0261</orcidid></search><sort><creationdate>20220524</creationdate><title>Influence of mutation in the regulatory domain of α-isopropylmalate synthase from Saccharomyces cerevisiae on its activity and feedback inhibition</title><author>Takagi, Hironobu ; Yamamoto, Kazuki ; Matsuo, Yoshifumi ; Furuie, Miki ; Kasayuki, Yasuha ; Ohtani, Rina ; Shiotani, Mizuki ; Hasegawa, Tetsuya ; Ohnishi, Toru ; Ohashi, Masataka ; Johzuka, Katsuki ; Kurata, Atsushi ; Uegaki, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c289t-8aad6b5ca1e828836e39ff51dd94b4d8500690a3c30253aa0ffaca1be7904e1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takagi, Hironobu</creatorcontrib><creatorcontrib>Yamamoto, Kazuki</creatorcontrib><creatorcontrib>Matsuo, Yoshifumi</creatorcontrib><creatorcontrib>Furuie, Miki</creatorcontrib><creatorcontrib>Kasayuki, Yasuha</creatorcontrib><creatorcontrib>Ohtani, Rina</creatorcontrib><creatorcontrib>Shiotani, Mizuki</creatorcontrib><creatorcontrib>Hasegawa, Tetsuya</creatorcontrib><creatorcontrib>Ohnishi, Toru</creatorcontrib><creatorcontrib>Ohashi, Masataka</creatorcontrib><creatorcontrib>Johzuka, Katsuki</creatorcontrib><creatorcontrib>Kurata, Atsushi</creatorcontrib><creatorcontrib>Uegaki, Koichi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioscience, biotechnology, and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takagi, Hironobu</au><au>Yamamoto, Kazuki</au><au>Matsuo, Yoshifumi</au><au>Furuie, Miki</au><au>Kasayuki, Yasuha</au><au>Ohtani, Rina</au><au>Shiotani, Mizuki</au><au>Hasegawa, Tetsuya</au><au>Ohnishi, Toru</au><au>Ohashi, Masataka</au><au>Johzuka, Katsuki</au><au>Kurata, Atsushi</au><au>Uegaki, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of mutation in the regulatory domain of α-isopropylmalate synthase from Saccharomyces cerevisiae on its activity and feedback inhibition</atitle><jtitle>Bioscience, biotechnology, and biochemistry</jtitle><addtitle>Biosci Biotechnol Biochem</addtitle><date>2022-05-24</date><risdate>2022</risdate><volume>86</volume><issue>6</issue><spage>755</spage><epage>762</epage><pages>755-762</pages><issn>1347-6947</issn><eissn>1347-6947</eissn><abstract>Isoamyl alcohol (i-AmOH) is produced from α-ketoisocaproate in the l-leucine biosynthetic pathway in yeast and controlled by the negative feedback regulation of α-isopropylmalate synthase (IPMS), which senses the accumulation of l-leucine. It is known that i-AmOH production increases when mutations in the regulatory domain reduce the susceptibility to feedback inhibition. However, the impact of mutations in this domain on the IPMS activity has not been examined. In this study, we obtained 5 IPMS mutants, encoding the LEU4 gene, N515D/S520P/S542F/A551D/A551V, that are tolerant to 5,5,5-trifluoro-dl-leucine. All mutant proteins were purified and examined for both IPMS activity and negative feedback activity by in vitro experiments. 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| title | Influence of mutation in the regulatory domain of α-isopropylmalate synthase from Saccharomyces cerevisiae on its activity and feedback inhibition |
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