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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9503987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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