β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>

β-Farnesene is value-added acyclic volatile sesquiterpene with wide applications in energy, industry, and agriculture. Producing high-value-added compounds from low-cost renewable feedstocks in engineered microbial cell factories is an environmentally friendly and economical process for β-farnesene...

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Main Authors: Haoran Bi, Chenchen Xv, Changsheng Su, Pan Feng, Changwei Zhang, Meng Wang, Yunming Fang, Tianwei Tan
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Fermentation
Subjects:
Online Access:https://www.mdpi.com/2311-5637/8/10/532
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author Haoran Bi
Chenchen Xv
Changsheng Su
Pan Feng
Changwei Zhang
Meng Wang
Yunming Fang
Tianwei Tan
author_facet Haoran Bi
Chenchen Xv
Changsheng Su
Pan Feng
Changwei Zhang
Meng Wang
Yunming Fang
Tianwei Tan
author_sort Haoran Bi
collection DOAJ
description β-Farnesene is value-added acyclic volatile sesquiterpene with wide applications in energy, industry, and agriculture. Producing high-value-added compounds from low-cost renewable feedstocks in engineered microbial cell factories is an environmentally friendly and economical process for β-farnesene biosynthesis. In this study, the potential for using engineered <i>Yarrowia lipolytica</i> to produce β-farnesene from lignocellulosic hydrolysate as the carbon source was investigated. An efficient biosynthetic pathway for β-farnesene production was established via iterative enhancement of multiple genes based on the high endogenous acetyl-CoA flux in <i>Yarrowia lipolytica.</i> Overexpression of mevalonate pathway genes and screening of β-farnesene synthase resulted in a β-farnesene titer of 245 mg L<sup>−1</sup> in glucose media. Additional copies of mevalonate pathway genes and enhanced expression of HMG-CoA reductase and β-farnesene synthase further increased the titer of β-farnesene to 470 mg L<sup>−1</sup>. In addition, by combining metabolic engineering strategies using the lignocellulosic hydrolysate utilization strategy, the addition of Mg<sup>2+</sup> promoted the production of β-farnesene, and the best-performing strain produced 7.38 ± 0.24 g L<sup>−1</sup> β-farnesene from lignocellulosic hydrolysate media in a 2 L fermenter after 144 h. This study shows great potential for the sustainable production of β-farnesene from lignocellulosic biomass via engineered <i>Yarrowia lipolytica</i>.
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spelling doaj.art-aecd64c5966747518b1e83841c6e63b82023-12-02T00:28:27ZengMDPI AGFermentation2311-56372022-10-0181053210.3390/fermentation8100532β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>Haoran Bi0Chenchen Xv1Changsheng Su2Pan Feng3Changwei Zhang4Meng Wang5Yunming Fang6Tianwei Tan7National Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, ChinaNational Energy Research Center for Biorefinery, Beijing University of Chemical Technology, Beijing 100029, Chinaβ-Farnesene is value-added acyclic volatile sesquiterpene with wide applications in energy, industry, and agriculture. Producing high-value-added compounds from low-cost renewable feedstocks in engineered microbial cell factories is an environmentally friendly and economical process for β-farnesene biosynthesis. In this study, the potential for using engineered <i>Yarrowia lipolytica</i> to produce β-farnesene from lignocellulosic hydrolysate as the carbon source was investigated. An efficient biosynthetic pathway for β-farnesene production was established via iterative enhancement of multiple genes based on the high endogenous acetyl-CoA flux in <i>Yarrowia lipolytica.</i> Overexpression of mevalonate pathway genes and screening of β-farnesene synthase resulted in a β-farnesene titer of 245 mg L<sup>−1</sup> in glucose media. Additional copies of mevalonate pathway genes and enhanced expression of HMG-CoA reductase and β-farnesene synthase further increased the titer of β-farnesene to 470 mg L<sup>−1</sup>. In addition, by combining metabolic engineering strategies using the lignocellulosic hydrolysate utilization strategy, the addition of Mg<sup>2+</sup> promoted the production of β-farnesene, and the best-performing strain produced 7.38 ± 0.24 g L<sup>−1</sup> β-farnesene from lignocellulosic hydrolysate media in a 2 L fermenter after 144 h. This study shows great potential for the sustainable production of β-farnesene from lignocellulosic biomass via engineered <i>Yarrowia lipolytica</i>.https://www.mdpi.com/2311-5637/8/10/532β-Farnesene<i>Yarrowia lipolytica</i>lignocellulosic hydrolysatemetabolic engineeringfed-batch fermentation
spellingShingle Haoran Bi
Chenchen Xv
Changsheng Su
Pan Feng
Changwei Zhang
Meng Wang
Yunming Fang
Tianwei Tan
β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
Fermentation
β-Farnesene
<i>Yarrowia lipolytica</i>
lignocellulosic hydrolysate
metabolic engineering
fed-batch fermentation
title β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
title_full β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
title_fullStr β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
title_full_unstemmed β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
title_short β-Farnesene Production from Low-Cost Glucose in Lignocellulosic Hydrolysate by Engineered <i>Yarrowia lipolytica</i>
title_sort β farnesene production from low cost glucose in lignocellulosic hydrolysate by engineered i yarrowia lipolytica i
topic β-Farnesene
<i>Yarrowia lipolytica</i>
lignocellulosic hydrolysate
metabolic engineering
fed-batch fermentation
url https://www.mdpi.com/2311-5637/8/10/532
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