{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:41:57Z","timestamp":1789094517591,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Melatonin synthesis by yeast has been described on several occasions, mainly in a fermentative context. However, the genetic determinants involved in its synthesis remain undefined. Understanding melatonin synthesis in yeast is important because it can provide insights into the broader mechanisms of indolamine production, which has implications for both basic biological research and industrial applications. Although two genes with\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyltransferase (NAT) activity (\n                    <jats:italic>PAA1<\/jats:italic>\n                    and\n                    <jats:italic>HPA2<\/jats:italic>\n                    ) have been identified in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    , these genes do not seem to be major contributors to the production of melatonin and other indolamines in yeast in vivo. In this study, we identified the uncharacterized gene YDR391C as the gene encoding a protein with NAT activity, herein named\n                    <jats:italic>IAT4<\/jats:italic>\n                    . By comparing different substrates using the purified Iat4, we found that the\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>m<\/jats:italic>\n                    <\/jats:sub>\n                    values were 353, 356, and 930\u2009\u00b5M towards 5\u2010methoxytryptamine, tryptamine, and serotonin, respectively. The substrate affinity of Iat4\u00a0towards serotonin was approximately five times higher than that reported for the previous homolog of the melatonin enzyme arylalkylamine\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyltransferase (\n                    <jats:italic>PAA1<\/jats:italic>\n                    ), suggesting that\n                    <jats:italic>IAT4<\/jats:italic>\n                    could play a more significant role in melatonin biosynthesis. This enhanced affinity could lead to more efficient production of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylserotonin, potentially improving yields in biotechnological applications. Finally, we demonstrate the conversion of serotonin into microbially\u2010produced\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylserotonin by overexpressing\n                    <jats:italic>IAT4<\/jats:italic>\n                    in a serotonin\u2010overproducing yeast strain at a titer of 14.5\u2009mg\/L. These findings represent the first steps towards the development of yeast strains optimized for the biological production of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylserotonin and related compounds, which might aid in studying the regulatory mechanisms and functions related to melatonin biosynthesis in\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    and other yeast species.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70053","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T08:42:13Z","timestamp":1746780133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>IAT4<\/i>\n                    , a New Indolamine\n                    <i>N<\/i>\n                    \u2010Acetyltransferase in\n                    <i>Saccharomyces cerevisiae<\/i>\n                    Involved in Melatonin Biosynthesis"],"prefix":"10.1111","volume":"77","author":[{"given":"Andr\u00e9s","family":"Planells\u2010C\u00e1rcel","sequence":"first","affiliation":[{"name":"Departamento de Biotecnolog\u00eda de Alimentos, Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA) Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"S\u00e1nchez\u2010Mart\u00ed","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda de Alimentos, Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA) Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mu\u00f1iz\u2010Calvo","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda de Alimentos, Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA) Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Valencia Spain"},{"name":"Chalmers University of Technology Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-0787","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Guillamon","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda de Alimentos, Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA) Consejo Superior de Investigaciones Cient\u00edficas (CSIC) Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12336"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00249"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01543a060"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01531a060"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)90600-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00969.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.32794\/mr11250029"},{"issue":"5","key":"e_1_2_9_9_1","first-page":"391","article-title":"Melatonin Immunoreactivity in the Photosynthetic Prokaryote Rhodospirillum rubrum: Implications for an Ancient Antioxidant System","volume":"41","author":"Manchester L. 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