{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:45:35Z","timestamp":1780562735706,"version":"3.54.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Sulfite plays an important role in beer flavor stability. Although breeding of bottom-fermenting\n            <jats:italic>Saccharomyces<\/jats:italic>\n            strains that produce high levels of SO\n            <jats:sub>2<\/jats:sub>\n            is desirable, it is complicated by the fact that undesirable H\n            <jats:sub>2<\/jats:sub>\n            S is produced as an intermediate in the same pathway. Here, we report the development of a high-level SO\n            <jats:sub>2<\/jats:sub>\n            -producing bottom-fermenting yeast strain by integrated metabolome and transcriptome analysis. This analysis revealed that\n            <jats:italic>O<\/jats:italic>\n            -acetylhomoserine (OAH) is the rate-limiting factor for the production of SO\n            <jats:sub>2<\/jats:sub>\n            and H\n            <jats:sub>2<\/jats:sub>\n            S. Appropriate genetic modifications were then introduced into a prototype strain to increase metabolic fluxes from aspartate to OAH and from sulfate to SO\n            <jats:sub>2<\/jats:sub>\n            , resulting in high SO\n            <jats:sub>2<\/jats:sub>\n            and low H\n            <jats:sub>2<\/jats:sub>\n            S production. Spontaneous mutants of an industrial strain that were resistant to both methionine and threonine analogs were then analyzed for similar metabolic fluxes. One promising mutant produced much higher levels of SO\n            <jats:sub>2<\/jats:sub>\n            than the parent but produced parental levels of H\n            <jats:sub>2<\/jats:sub>\n            S.\n          <\/jats:p>","DOI":"10.1128\/aem.01781-07","type":"journal-article","created":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T02:37:03Z","timestamp":1204339023000},"page":"2787-2796","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Development of Bottom-Fermenting\n            <i>Saccharomyces<\/i>\n            Strains That Produce High SO\n            <sub>2<\/sub>\n            Levels, Using Integrated Metabolome and Transcriptome Analysis"],"prefix":"10.1128","volume":"74","author":[{"given":"Satoshi","family":"Yoshida","sequence":"first","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Imoto","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka-shi, Yamagata 997-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiko","family":"Minato","sequence":"additional","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Oouchi","sequence":"additional","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Research Laboratories for Brewing, KIRIN Brewery Co., Ltd., 1-17-1 Namamugi Tsurumi-ku, Yokohama-shi, Kanagawa 230-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Imai","sequence":"additional","affiliation":[{"name":"Research Laboratories for Brewing, KIRIN Brewery Co., Ltd., 1-17-1 Namamugi Tsurumi-ku, Yokohama-shi, Kanagawa 230-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuji","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tomita","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka-shi, Yamagata 997-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Soga","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Keio University, 246-2 Mizukami Kakuganji, Tsuruoka-shi, Yamagata 997-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Central Laboratories for Frontier Technology, KIRIN Holdings Co., Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/15362310260256882"},{"key":"e_1_3_1_3_2","first-page":"216","volume":"92","year":"1987","unstructured":"Bilinski, C. A., I. Russell, and G. G. Stewart. 1987. Physiological requirements for induction of sporulation in lager yeast. J. Inst. Brew.92:216-219.","journal-title":"J. Inst. Brew."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00267406"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.849"},{"key":"e_1_3_1_6_2","first-page":"35","volume":"62","year":"2004","unstructured":"Duan, W., F. A. Roddick, V. J. Higgins, and P. J. Rogers. 2004. A parallel analysis of H2S and SO2 formation by brewing yeast in response to sulfur-containing amino acids and ammonium ions. J. Am. Soc. Brew. Chem.62:35-41.","journal-title":"J. Am. Soc. Brew. Chem."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.65.1.110-116.1999"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/81137"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(199605)12:6<593::AID-YEA593>3.0.CO;2-B"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(199608)12:10<939::AID-YEA988>3.0.CO;2-L"},{"key":"e_1_3_1_11_2","first-page":"347","year":"1989","unstructured":"Gyllang, H., M. Winge, and C. Korch. 1989. Regulation of SO2 formation during fermentation, p. 347-354. In European Brewery Convention, Proceedings of the 22nd Congress. 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Reduction of hydrogen sulfide production in brewing yeast by constitutive expression of MET25 gene. J. Am. Soc. Brew. Chem.53:58-62.","journal-title":"J. Am. Soc. Brew. Chem."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0061(200007)16:10<881::AID-YEA576>3.0.CO;2-3"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.58.5.1677-1682.1992"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1081\/DCT-120014789"},{"key":"e_1_3_1_22_2","unstructured":"Methods in yeast genetics: a laboratory course manual. 1990"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0922-338X(91)90269-M"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac990976y"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac020064n"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr034020m"},{"key":"e_1_3_1_27_2","first-page":"29","volume":"26","year":"1980","unstructured":"Takahashi, T., M. Hojito, and K. Sakai. 1980. Genes controlling hydrogen-sulfide production in Saccharomyces cerevisiae. Bull. Brew. Sci.26:29-36.","journal-title":"Bull. Brew. Sci."},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0061(200010)16:14<1335::AID-YEA623>3.0.CO;2-P"},{"key":"e_1_3_1_29_2","first-page":"130","volume":"50","year":"1992","unstructured":"Tezuka, H., T. Mori, Y. Okumura, K. Kitabatake, and Y. Tsumura. 1992. Cloning of a gene suppressing hydrogen sulfide production by Saccharomyces cerevisiae and its expression in a brewing yeast. J. Am. Soc. Brew. Chem.50:130-133.","journal-title":"J. Am. Soc. Brew. Chem."},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.61.4.503-532.1997"},{"key":"e_1_3_1_31_2","first-page":"358","year":"1998","unstructured":"Vaughan-Martini, A., and A. Martini. 1998. A taxonomic study: Saccharomyces Myen ex Reessm, p. 358-371. In C. P. Kurtzman and J. W. Fell (ed.), The yeasts. 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