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Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica

Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a “push–pull” strategy was adopted to increase ta...

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Autores principales: Xu, Man, Xie, Wenliang, Luo, Zhen, Li, Chun-Xiu, Hua, Qiang, Xu, Jianhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196790/
https://www.ncbi.nlm.nih.gov/pubmed/37215159
http://dx.doi.org/10.1016/j.synbio.2023.04.002
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author Xu, Man
Xie, Wenliang
Luo, Zhen
Li, Chun-Xiu
Hua, Qiang
Xu, Jianhe
author_facet Xu, Man
Xie, Wenliang
Luo, Zhen
Li, Chun-Xiu
Hua, Qiang
Xu, Jianhe
author_sort Xu, Man
collection PubMed
description Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a “push–pull” strategy was adopted to increase taxadiene production by 234%. Then taxadiene synthase was fused with five solubilizing tags respectively, leading a maximum increase of 62.3% in taxadiene production when fused with SUMO. Subsequently, a multi-copy iterative integration method was used to further increase taxadiene titer, achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration. Finally, the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentation conditions. This is the first report of taxadiene biosynthesis accomplished in Y. lipolytica, serving as a good example for the sustainable production of taxadiene and other terpenoids in this oleaginous yeast.
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spelling pubmed-101967902023-05-20 Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica Xu, Man Xie, Wenliang Luo, Zhen Li, Chun-Xiu Hua, Qiang Xu, Jianhe Synth Syst Biotechnol Original Research Article Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a “push–pull” strategy was adopted to increase taxadiene production by 234%. Then taxadiene synthase was fused with five solubilizing tags respectively, leading a maximum increase of 62.3% in taxadiene production when fused with SUMO. Subsequently, a multi-copy iterative integration method was used to further increase taxadiene titer, achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration. Finally, the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentation conditions. This is the first report of taxadiene biosynthesis accomplished in Y. lipolytica, serving as a good example for the sustainable production of taxadiene and other terpenoids in this oleaginous yeast. KeAi Publishing 2023-04-26 /pmc/articles/PMC10196790/ /pubmed/37215159 http://dx.doi.org/10.1016/j.synbio.2023.04.002 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Xu, Man
Xie, Wenliang
Luo, Zhen
Li, Chun-Xiu
Hua, Qiang
Xu, Jianhe
Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title_full Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title_fullStr Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title_full_unstemmed Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title_short Improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in Yarrowia lipolytica
title_sort improving solubility and copy number of taxadiene synthase to enhance the titer of taxadiene in yarrowia lipolytica
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196790/
https://www.ncbi.nlm.nih.gov/pubmed/37215159
http://dx.doi.org/10.1016/j.synbio.2023.04.002
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