Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>

Z,Z-farnesol (Z,Z-FOH), the all-<i>cis</i> isomer of farnesol, holds enormous potential for application in cosmetics, daily chemicals, and pharmaceuticals. In this study, we aimed to metabolically engineer <i>Escherichia coli</i> to produce Z,Z-FOH. First, we tested five Z,Z-...

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Main Authors: Mengyang Lei, Zetian Qiu, Leilei Guan, Zheng Xiang, Guang-Rong Zhao
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/11/6/1583
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author Mengyang Lei
Zetian Qiu
Leilei Guan
Zheng Xiang
Guang-Rong Zhao
author_facet Mengyang Lei
Zetian Qiu
Leilei Guan
Zheng Xiang
Guang-Rong Zhao
author_sort Mengyang Lei
collection DOAJ
description Z,Z-farnesol (Z,Z-FOH), the all-<i>cis</i> isomer of farnesol, holds enormous potential for application in cosmetics, daily chemicals, and pharmaceuticals. In this study, we aimed to metabolically engineer <i>Escherichia coli</i> to produce Z,Z-FOH. First, we tested five Z,Z-farnesyl diphosphate (Z,Z-FPP) synthases that catalyze neryl diphosphate to form Z,Z-FPP in <i>E. coli</i>. Furthermore, we screened thirteen phosphatases that could facilitate the dephosphorylation of Z,Z-FPP to produce Z,Z-FOH. Finally, through site-directed mutagenesis of <i>cis</i>-prenyltransferase, the optimal mutant strain was able to produce 572.13 mg/L Z,Z-FOH by batch fermentation in a shake flask. This achievement represents the highest reported titer of Z,Z-FOH in microbes to date. Notably, this is the first report on the de novo biosynthesis of Z,Z-FOH in <i>E. coli</i>. This work represents a promising step toward developing synthetic <i>E. coli</i> cell factories for the de novo biosynthesis of Z,Z-FOH and other <i>cis</i>-configuration terpenoids.
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spelling doaj.art-5f1eee264b0345f298cb2d27b6b56f672023-11-18T11:43:57ZengMDPI AGMicroorganisms2076-26072023-06-01116158310.3390/microorganisms11061583Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>Mengyang Lei0Zetian Qiu1Leilei Guan2Zheng Xiang3Guang-Rong Zhao4Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaFrontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaFrontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaState Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, ChinaFrontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin 300350, ChinaZ,Z-farnesol (Z,Z-FOH), the all-<i>cis</i> isomer of farnesol, holds enormous potential for application in cosmetics, daily chemicals, and pharmaceuticals. In this study, we aimed to metabolically engineer <i>Escherichia coli</i> to produce Z,Z-FOH. First, we tested five Z,Z-farnesyl diphosphate (Z,Z-FPP) synthases that catalyze neryl diphosphate to form Z,Z-FPP in <i>E. coli</i>. Furthermore, we screened thirteen phosphatases that could facilitate the dephosphorylation of Z,Z-FPP to produce Z,Z-FOH. Finally, through site-directed mutagenesis of <i>cis</i>-prenyltransferase, the optimal mutant strain was able to produce 572.13 mg/L Z,Z-FOH by batch fermentation in a shake flask. This achievement represents the highest reported titer of Z,Z-FOH in microbes to date. Notably, this is the first report on the de novo biosynthesis of Z,Z-FOH in <i>E. coli</i>. This work represents a promising step toward developing synthetic <i>E. coli</i> cell factories for the de novo biosynthesis of Z,Z-FOH and other <i>cis</i>-configuration terpenoids.https://www.mdpi.com/2076-2607/11/6/1583(2Z,6Z)-farnesolenzyme engineeringmetabolic engineering<i>Escherichia coli</i>synthetic biology
spellingShingle Mengyang Lei
Zetian Qiu
Leilei Guan
Zheng Xiang
Guang-Rong Zhao
Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
Microorganisms
(2Z,6Z)-farnesol
enzyme engineering
metabolic engineering
<i>Escherichia coli</i>
synthetic biology
title Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
title_full Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
title_fullStr Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
title_full_unstemmed Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
title_short Metabolic Engineering for Efficient Production of Z,Z-Farnesol in <i>E. coli</i>
title_sort metabolic engineering for efficient production of z z farnesol in i e coli i
topic (2Z,6Z)-farnesol
enzyme engineering
metabolic engineering
<i>Escherichia coli</i>
synthetic biology
url https://www.mdpi.com/2076-2607/11/6/1583
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