IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis

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...

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Detalhes bibliográficos
Autores: Planells Cárcel, Andrés, Sánchez Martí, Sandra, Muñiz Calvo, Sara, Guillamón, José Manuel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/389837
Acesso em linha:http://hdl.handle.net/10261/389837
https://api.elsevier.com/content/abstract/scopus_id/105004701530
Access Level:acceso abierto
Palavra-chave:5‐methoxytryptamine
S. cerevisiae
Melatonin
Serotonin
Serotonin N‐acetyltransferase
Saccharomyces cerevisiae
serotonin
melatonin
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dc.title.none.fl_str_mv IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
title IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
spellingShingle IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
Planells Cárcel, Andrés
5‐methoxytryptamine
S. cerevisiae
Melatonin
Serotonin
Serotonin N‐acetyltransferase
Saccharomyces cerevisiae
serotonin
melatonin
title_short IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
title_full IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
title_fullStr IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
title_full_unstemmed IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
title_sort IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis
dc.creator.none.fl_str_mv Planells Cárcel, Andrés
Sánchez Martí, Sandra
Muñiz Calvo, Sara
Guillamón, José Manuel
author Planells Cárcel, Andrés
author_facet Planells Cárcel, Andrés
Sánchez Martí, Sandra
Muñiz Calvo, Sara
Guillamón, José Manuel
author_role author
author2 Sánchez Martí, Sandra
Muñiz Calvo, Sara
Guillamón, José Manuel
author2_role author
author
author
dc.contributor.none.fl_str_mv Generalitat Valenciana
European Commission
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Guillamón, José Manuel [0000-0001-5414-0787]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv 5‐methoxytryptamine
S. cerevisiae
Melatonin
Serotonin
Serotonin N‐acetyltransferase
Saccharomyces cerevisiae
serotonin
melatonin
topic 5‐methoxytryptamine
S. cerevisiae
Melatonin
Serotonin
Serotonin N‐acetyltransferase
Saccharomyces cerevisiae
serotonin
melatonin
description 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-acetyltransferase (NAT) activity (PAA1 and HPA2) have been identified in Saccharomyces cerevisiae, 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 IAT4. By comparing different substrates using the purified Iat4, we found that the Km values were 353, 356, and 930 µM towards 5-methoxytryptamine, tryptamine, and serotonin, respectively. The substrate affinity of Iat4 towards serotonin was approximately five times higher than that reported for the previous homolog of the melatonin enzyme arylalkylamine N-acetyltransferase (PAA1), suggesting that IAT4 could play a more significant role in melatonin biosynthesis. This enhanced affinity could lead to more efficient production of N-acetylserotonin, potentially improving yields in biotechnological applications. Finally, we demonstrate the conversion of serotonin into microbially-produced N-acetylserotonin by overexpressing IAT4 in a serotonin-overproducing yeast strain at a titer of 14.5 mg/L. These findings represent the first steps towards the development of yeast strains optimized for the biological production of N-acetylserotonin and related compounds, which might aid in studying the regulatory mechanisms and functions related to melatonin biosynthesis in S. cerevisiae and other yeast species.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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info:eu-repo/semantics/publishedVersion
format article
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/389837
https://api.elsevier.com/content/abstract/scopus_id/105004701530
url http://hdl.handle.net/10261/389837
https://api.elsevier.com/content/abstract/scopus_id/105004701530
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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Journal of pineal research
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1111/jpi.70053
https://doi.org/10.1111/jpi.70053
Sí
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dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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spelling IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin BiosynthesisPlanells Cárcel, AndrésSánchez Martí, SandraMuñiz Calvo, SaraGuillamón, José Manuel5‐methoxytryptamineS. cerevisiaeMelatoninSerotoninSerotonin N‐acetyltransferaseSaccharomyces cerevisiaeserotoninmelatoninMelatonin 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-acetyltransferase (NAT) activity (PAA1 and HPA2) have been identified in Saccharomyces cerevisiae, 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 IAT4. By comparing different substrates using the purified Iat4, we found that the Km values were 353, 356, and 930 µM towards 5-methoxytryptamine, tryptamine, and serotonin, respectively. The substrate affinity of Iat4 towards serotonin was approximately five times higher than that reported for the previous homolog of the melatonin enzyme arylalkylamine N-acetyltransferase (PAA1), suggesting that IAT4 could play a more significant role in melatonin biosynthesis. This enhanced affinity could lead to more efficient production of N-acetylserotonin, potentially improving yields in biotechnological applications. Finally, we demonstrate the conversion of serotonin into microbially-produced N-acetylserotonin by overexpressing IAT4 in a serotonin-overproducing yeast strain at a titer of 14.5 mg/L. These findings represent the first steps towards the development of yeast strains optimized for the biological production of N-acetylserotonin and related compounds, which might aid in studying the regulatory mechanisms and functions related to melatonin biosynthesis in S. cerevisiae and other yeast species.This study was funded by MCIN/AEI/10.13039/501100011033, grant number PID2022-142748OB-I00 and TED2021-132386B-I00, and by Generalitat Valenciana, grant number AGROALNEXT/2022/049. A.P.C. is thankful for the FPU19/02060 grant funded by “ESF Investing in your future”. Authors acknowledge the award of the Spanish government MCIN/AEI to the IATA-CSIC as Center of Excellence “Severo Ochoa” (CEX2021-001189-S/MICIU/AEI/10.13039/501100011033).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)Peer reviewedJohn Wiley & SonsGeneralitat ValencianaEuropean CommissionMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Guillamón, José Manuel [0000-0001-5414-0787]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/PDFhttp://hdl.handle.net/10261/389837https://api.elsevier.com/content/abstract/scopus_id/105004701530reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001189-Sinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-142748OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/TED2021-132386B-I00Journal of pineal researchThe underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1111/jpi.70053https://doi.org/10.1111/jpi.70053Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3898372026-05-22T06:33:51Z
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