Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker

IntroductionL-valine is commonly utilized in cosmetics, pharmaceuticals, food additives, and animal feeds. The selection and breeding of high-yielding, low-cost, and genetically stable production strains have become a key objective in the L-valine production industry.MethodsUsing Escherichia coli DB...

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Main Authors: Bowen Du, Sheng Gao, Daixue Kou, Yinuo Li, Dan Li, Yongsheng Cao, Cuiping Yang, Chuanzhuang Guo, Jianbin Wang, Junqing Wang, Nan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1627242/full
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author Bowen Du
Bowen Du
Sheng Gao
Sheng Gao
Daixue Kou
Daixue Kou
Yinuo Li
Yinuo Li
Dan Li
Dan Li
Yongsheng Cao
Yongsheng Cao
Cuiping Yang
Chuanzhuang Guo
Jianbin Wang
Junqing Wang
Junqing Wang
Nan Li
Nan Li
author_facet Bowen Du
Bowen Du
Sheng Gao
Sheng Gao
Daixue Kou
Daixue Kou
Yinuo Li
Yinuo Li
Dan Li
Dan Li
Yongsheng Cao
Yongsheng Cao
Cuiping Yang
Chuanzhuang Guo
Jianbin Wang
Junqing Wang
Junqing Wang
Nan Li
Nan Li
author_sort Bowen Du
collection DOAJ
description IntroductionL-valine is commonly utilized in cosmetics, pharmaceuticals, food additives, and animal feeds. The selection and breeding of high-yielding, low-cost, and genetically stable production strains have become a key objective in the L-valine production industry.MethodsUsing Escherichia coli DB-1-1, we developed a screening marker LESG associated with intracellular L-valine levels by choosing GTC, a less common codon for L-valine, in place of all L-valine codons. The artificial LESG was then ligated into pUC-57 and transformed into competent E. coli DB-1-1 cells with the rare L-valine codon. After conducting atmospheric and room-temperature plasma mutagenesis cultures, mutants that displayed elevated fluorescence were sorted using flow cytometry. After sorting the 240 strains. We sorted out 143 highly fluorescent strains, and the sorting efficiency reached 59.5%.ResultsFermentation results showed that the mutant strains with increased fluorescence intensity had an improved L-valine fermentation titer (23.1%) and a higher screening positivity rate (62.5%) than that of the wild-type strain. The maximum titer of valine at 24 h was 84.1 g/L.ConclusionThis approach offers a more comprehensive and effective method for identifying high-yielding L-valine bacterial strains.
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series Frontiers in Microbiology
spelling doaj-art-48a881ccbb4146e38e995efd1b0168c32025-08-20T04:01:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16272421627242Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening markerBowen Du0Bowen Du1Sheng Gao2Sheng Gao3Daixue Kou4Daixue Kou5Yinuo Li6Yinuo Li7Dan Li8Dan Li9Yongsheng Cao10Yongsheng Cao11Cuiping Yang12Chuanzhuang Guo13Jianbin Wang14Junqing Wang15Junqing Wang16Nan Li17Nan Li18State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaDongxiao Bioengineering (Shandong) Co., Ltd., Zhucheng, ChinaDongxiao Bioengineering (Shandong) Co., Ltd., Zhucheng, ChinaDongxiao Bioengineering (Shandong) Co., Ltd., Zhucheng, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaState Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, ChinaSchool of Bioengineering, Qilu University of Technology, Jinan, Shandong, ChinaIntroductionL-valine is commonly utilized in cosmetics, pharmaceuticals, food additives, and animal feeds. The selection and breeding of high-yielding, low-cost, and genetically stable production strains have become a key objective in the L-valine production industry.MethodsUsing Escherichia coli DB-1-1, we developed a screening marker LESG associated with intracellular L-valine levels by choosing GTC, a less common codon for L-valine, in place of all L-valine codons. The artificial LESG was then ligated into pUC-57 and transformed into competent E. coli DB-1-1 cells with the rare L-valine codon. After conducting atmospheric and room-temperature plasma mutagenesis cultures, mutants that displayed elevated fluorescence were sorted using flow cytometry. After sorting the 240 strains. We sorted out 143 highly fluorescent strains, and the sorting efficiency reached 59.5%.ResultsFermentation results showed that the mutant strains with increased fluorescence intensity had an improved L-valine fermentation titer (23.1%) and a higher screening positivity rate (62.5%) than that of the wild-type strain. The maximum titer of valine at 24 h was 84.1 g/L.ConclusionThis approach offers a more comprehensive and effective method for identifying high-yielding L-valine bacterial strains.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1627242/fullEscherichia colihigh-throughput screeningrare codonL-valinefluorescent protein
spellingShingle Bowen Du
Bowen Du
Sheng Gao
Sheng Gao
Daixue Kou
Daixue Kou
Yinuo Li
Yinuo Li
Dan Li
Dan Li
Yongsheng Cao
Yongsheng Cao
Cuiping Yang
Chuanzhuang Guo
Jianbin Wang
Junqing Wang
Junqing Wang
Nan Li
Nan Li
Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
Frontiers in Microbiology
Escherichia coli
high-throughput screening
rare codon
L-valine
fluorescent protein
title Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
title_full Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
title_fullStr Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
title_full_unstemmed Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
title_short Construction and screening of L-valine high-yielding Escherichia coli using an artificial screening marker
title_sort construction and screening of l valine high yielding escherichia coli using an artificial screening marker
topic Escherichia coli
high-throughput screening
rare codon
L-valine
fluorescent protein
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1627242/full
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