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Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol

Menthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. The...

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Autores principales: Lv, Xueqin, Zhou, Xuan, Ma, Jun, Tao, Mengrui, Liu, Yanfeng, Li, Jianghua, Du, Guocheng, Liu, Long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503987/
https://www.ncbi.nlm.nih.gov/pubmed/36135706
http://dx.doi.org/10.3390/jof8090982
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author Lv, Xueqin
Zhou, Xuan
Ma, Jun
Tao, Mengrui
Liu, Yanfeng
Li, Jianghua
Du, Guocheng
Liu, Long
author_facet Lv, Xueqin
Zhou, Xuan
Ma, Jun
Tao, Mengrui
Liu, Yanfeng
Li, Jianghua
Du, Guocheng
Liu, Long
author_sort Lv, Xueqin
collection PubMed
description Menthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. Therefore, this study attempted to realize the de novo synthesis of menthol through microbial fermentation. First, through heterologous expression and subcellular localization observation, a synthetic route from glucose to (−)-menthol was successfully designed and constructed in Saccharomyces cerevisiae. Then, the mevalonate (MVA) pathway was enhanced, and the expression of farnesyl diphosphate synthase (ERG20) was dynamically regulated to improve the synthesis of D-limonene, a key precursor of (−)-menthol. Shake flask fermentation results showed that the D-limonene titer of the recombinant strain reached 459.59 mg/L. Next, the synthesis pathway from D-limonene to (−)-menthol was strengthened, and the fermentation medium was optimized. The (−)-menthol titer of 6.28 mg/L was obtained, implying that the de novo synthesis of menthol was successfully realized for the first time. This study provides a good foundation for the synthesis of menthol through microbial fermentation.
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spelling pubmed-95039872022-09-24 Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol Lv, Xueqin Zhou, Xuan Ma, Jun Tao, Mengrui Liu, Yanfeng Li, Jianghua Du, Guocheng Liu, Long J Fungi (Basel) Article Menthol, a high-value commodity monoterpenoid chemical, holds an important market share commercially because of its distinct functions. The menthol on the market mainly originates from plant extraction, which is facing challenges such as the seasonal fluctuations and long growth cycle of plants. Therefore, this study attempted to realize the de novo synthesis of menthol through microbial fermentation. First, through heterologous expression and subcellular localization observation, a synthetic route from glucose to (−)-menthol was successfully designed and constructed in Saccharomyces cerevisiae. Then, the mevalonate (MVA) pathway was enhanced, and the expression of farnesyl diphosphate synthase (ERG20) was dynamically regulated to improve the synthesis of D-limonene, a key precursor of (−)-menthol. Shake flask fermentation results showed that the D-limonene titer of the recombinant strain reached 459.59 mg/L. Next, the synthesis pathway from D-limonene to (−)-menthol was strengthened, and the fermentation medium was optimized. The (−)-menthol titer of 6.28 mg/L was obtained, implying that the de novo synthesis of menthol was successfully realized for the first time. This study provides a good foundation for the synthesis of menthol through microbial fermentation. MDPI 2022-09-19 /pmc/articles/PMC9503987/ /pubmed/36135706 http://dx.doi.org/10.3390/jof8090982 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lv, Xueqin
Zhou, Xuan
Ma, Jun
Tao, Mengrui
Liu, Yanfeng
Li, Jianghua
Du, Guocheng
Liu, Long
Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title_full Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title_fullStr Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title_full_unstemmed Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title_short Engineered Saccharomyces cerevisiae for the De Novo Biosynthesis of (−)-Menthol
title_sort engineered saccharomyces cerevisiae for the de novo biosynthesis of (−)-menthol
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503987/
https://www.ncbi.nlm.nih.gov/pubmed/36135706
http://dx.doi.org/10.3390/jof8090982
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