Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories

Summary The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable...

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Autores principales:	Natalja Kulagina, Grégory Guirimand, Céline Melin, Pamela Lemos‐Cruz, Ines Carqueijeiro, Johan‐Owen De Craene, Audrey Oudin, Vladimir Heredia, Konstantinos Koudounas, Marianne Unlubayir, Arnaud Lanoue, Nadine Imbault, Benoit St‐Pierre, Nicolas Papon, Marc Clastre, Nathalie Giglioli‐Guivarc’h, Jillian Marc, Sébastien Besseau, Vincent Courdavault
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/60e784bff10b43a9a3cb622a92581120
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spelling	oai:doaj.org-article:60e784bff10b43a9a3cb622a925811202021-11-18T15:39:53ZEnhanced bioproduction of anticancer precursor vindoline by yeast cell factories1751-791510.1111/1751-7915.13898https://doaj.org/article/60e784bff10b43a9a3cb622a925811202021-11-01T00:00:00Zhttps://doi.org/10.1111/1751-7915.13898https://doaj.org/toc/1751-7915Summary The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable and massive manufacturing. Here, we developed and optimized yeast cell factories efficiently converting tabersonine to vindoline, a precursor of the major anticancer alkaloids vinblastine and vincristine. First, fine‐tuning of heterologous gene copies restrained side metabolites synthesis towards vindoline production. Tabersonine to vindoline bioconversion was further enhanced through a rational medium optimization (pH, composition) and a sequential feeding strategy. Finally, a vindoline titre of 266 mg l−1 (88% yield) was reached in an optimized fed‐batch bioreactor. This precursor‐directed synthesis of vindoline thus paves the way towards future industrial bioproduction through the valorization of abundant tabersonine resources.Natalja KulaginaGrégory GuirimandCéline MelinPamela Lemos‐CruzInes CarqueijeiroJohan‐Owen De CraeneAudrey OudinVladimir HerediaKonstantinos KoudounasMarianne UnlubayirArnaud LanoueNadine ImbaultBenoit St‐PierreNicolas PaponMarc ClastreNathalie Giglioli‐Guivarc’hJillian MarcSébastien BesseauVincent CourdavaultWileyarticleBiotechnologyTP248.13-248.65ENMicrobial Biotechnology, Vol 14, Iss 6, Pp 2693-2699 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65
spellingShingle	Biotechnology TP248.13-248.65 Natalja Kulagina Grégory Guirimand Céline Melin Pamela Lemos‐Cruz Ines Carqueijeiro Johan‐Owen De Craene Audrey Oudin Vladimir Heredia Konstantinos Koudounas Marianne Unlubayir Arnaud Lanoue Nadine Imbault Benoit St‐Pierre Nicolas Papon Marc Clastre Nathalie Giglioli‐Guivarc’h Jillian Marc Sébastien Besseau Vincent Courdavault Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
description	Summary The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable and massive manufacturing. Here, we developed and optimized yeast cell factories efficiently converting tabersonine to vindoline, a precursor of the major anticancer alkaloids vinblastine and vincristine. First, fine‐tuning of heterologous gene copies restrained side metabolites synthesis towards vindoline production. Tabersonine to vindoline bioconversion was further enhanced through a rational medium optimization (pH, composition) and a sequential feeding strategy. Finally, a vindoline titre of 266 mg l−1 (88% yield) was reached in an optimized fed‐batch bioreactor. This precursor‐directed synthesis of vindoline thus paves the way towards future industrial bioproduction through the valorization of abundant tabersonine resources.
format	article
author	Natalja Kulagina Grégory Guirimand Céline Melin Pamela Lemos‐Cruz Ines Carqueijeiro Johan‐Owen De Craene Audrey Oudin Vladimir Heredia Konstantinos Koudounas Marianne Unlubayir Arnaud Lanoue Nadine Imbault Benoit St‐Pierre Nicolas Papon Marc Clastre Nathalie Giglioli‐Guivarc’h Jillian Marc Sébastien Besseau Vincent Courdavault
author_facet	Natalja Kulagina Grégory Guirimand Céline Melin Pamela Lemos‐Cruz Ines Carqueijeiro Johan‐Owen De Craene Audrey Oudin Vladimir Heredia Konstantinos Koudounas Marianne Unlubayir Arnaud Lanoue Nadine Imbault Benoit St‐Pierre Nicolas Papon Marc Clastre Nathalie Giglioli‐Guivarc’h Jillian Marc Sébastien Besseau Vincent Courdavault
author_sort	Natalja Kulagina
title	Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
title_short	Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
title_full	Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
title_fullStr	Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
title_full_unstemmed	Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
title_sort	enhanced bioproduction of anticancer precursor vindoline by yeast cell factories
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/60e784bff10b43a9a3cb622a92581120
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Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories

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