Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12

In this study, we identified eight multicopy suppressors (yhjE, sdaC, ydgI, alaE, ychE, yqeG, proP, and yjeM) and three distinct classes of chromosomal mutations (lrp, marC, and cycA) capable of complementing the growth defect caused by threonine uptake deficiency in the sstT tdcC livKHMGF brnQ thrP...

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Main Authors: Dmitrii M. Bubnov, Andrey A. Khozov, Tatiana V. Vybornaya, Agnessa A. Stepanova, Sergey V. Molev, Olga E. Melkina, Gennadii A. Badun, Maria G. Chernysheva, Ilia A. Skob, Alexander I. Netrusov, Sergey P. Sineoky
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1579813/full
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author Dmitrii M. Bubnov
Andrey A. Khozov
Andrey A. Khozov
Tatiana V. Vybornaya
Agnessa A. Stepanova
Agnessa A. Stepanova
Sergey V. Molev
Sergey V. Molev
Olga E. Melkina
Gennadii A. Badun
Maria G. Chernysheva
Ilia A. Skob
Alexander I. Netrusov
Sergey P. Sineoky
author_facet Dmitrii M. Bubnov
Andrey A. Khozov
Andrey A. Khozov
Tatiana V. Vybornaya
Agnessa A. Stepanova
Agnessa A. Stepanova
Sergey V. Molev
Sergey V. Molev
Olga E. Melkina
Gennadii A. Badun
Maria G. Chernysheva
Ilia A. Skob
Alexander I. Netrusov
Sergey P. Sineoky
author_sort Dmitrii M. Bubnov
collection DOAJ
description In this study, we identified eight multicopy suppressors (yhjE, sdaC, ydgI, alaE, ychE, yqeG, proP, and yjeM) and three distinct classes of chromosomal mutations (lrp, marC, and cycA) capable of complementing the growth defect caused by threonine uptake deficiency in the sstT tdcC livKHMGF brnQ thrP strain. YhjE, SdaC, YdgI, AlaE, mutant MarC, and CycA exhibited measurable threonine-specific uptake activity in the in vitro assay. Phenotypic assays revealed that YhjE and SdaC were the main entry points for threonine in a strain lacking major threonine-specific permeases. A derivative of the threonine-auxotrophic sstT tdcC livKHMGF brnQ thrP mutant, harboring deletions of eight multicopy suppressors, exhibited significantly reduced fitness at subsaturating threonine concentrations and improved fitness at toxic threonine concentrations, indicating a defect in membrane permeability. These results may help guide the effective construction of threonine-producing strains, extend knowledge on the substrate preferences of SdaC, AlaE, and ProP, and provide clues for further studies on the exact substrate range of YhjE, YdgI, YjeM, YchE, MarC, and YqeG whose physiologically relevant functions have not yet been established.
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publisher Frontiers Media S.A.
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series Frontiers in Microbiology
spelling doaj-art-da59991387ae4d779a94a4d90d1272fc2025-08-20T03:06:43ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15798131579813Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12Dmitrii M. Bubnov0Andrey A. Khozov1Andrey A. Khozov2Tatiana V. Vybornaya3Agnessa A. Stepanova4Agnessa A. Stepanova5Sergey V. Molev6Sergey V. Molev7Olga E. Melkina8Gennadii A. Badun9Maria G. Chernysheva10Ilia A. Skob11Alexander I. Netrusov12Sergey P. Sineoky13National Research Centre “Kurchatov Institute”, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaDepartment of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaDepartment of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaDepartment of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaDepartment of Radiochemistry, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, RussiaDepartment of Radiochemistry, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, RussiaDepartment of Genetics, Faculty of Biology, Lomonosov Moscow State University, Moscow, RussiaDepartment of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, RussiaNational Research Centre “Kurchatov Institute”, Moscow, RussiaIn this study, we identified eight multicopy suppressors (yhjE, sdaC, ydgI, alaE, ychE, yqeG, proP, and yjeM) and three distinct classes of chromosomal mutations (lrp, marC, and cycA) capable of complementing the growth defect caused by threonine uptake deficiency in the sstT tdcC livKHMGF brnQ thrP strain. YhjE, SdaC, YdgI, AlaE, mutant MarC, and CycA exhibited measurable threonine-specific uptake activity in the in vitro assay. Phenotypic assays revealed that YhjE and SdaC were the main entry points for threonine in a strain lacking major threonine-specific permeases. A derivative of the threonine-auxotrophic sstT tdcC livKHMGF brnQ thrP mutant, harboring deletions of eight multicopy suppressors, exhibited significantly reduced fitness at subsaturating threonine concentrations and improved fitness at toxic threonine concentrations, indicating a defect in membrane permeability. These results may help guide the effective construction of threonine-producing strains, extend knowledge on the substrate preferences of SdaC, AlaE, and ProP, and provide clues for further studies on the exact substrate range of YhjE, YdgI, YjeM, YchE, MarC, and YqeG whose physiologically relevant functions have not yet been established.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1579813/fullEscherichia colil-threonine uptaketransmembrane transportamino acid transportermembrane proteins
spellingShingle Dmitrii M. Bubnov
Andrey A. Khozov
Andrey A. Khozov
Tatiana V. Vybornaya
Agnessa A. Stepanova
Agnessa A. Stepanova
Sergey V. Molev
Sergey V. Molev
Olga E. Melkina
Gennadii A. Badun
Maria G. Chernysheva
Ilia A. Skob
Alexander I. Netrusov
Sergey P. Sineoky
Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
Frontiers in Microbiology
Escherichia coli
l-threonine uptake
transmembrane transport
amino acid transporter
membrane proteins
title Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
title_full Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
title_fullStr Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
title_full_unstemmed Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
title_short Multiple routes for non-physiological l-threonine uptake in Escherichia coli K-12
title_sort multiple routes for non physiological l threonine uptake in escherichia coli k 12
topic Escherichia coli
l-threonine uptake
transmembrane transport
amino acid transporter
membrane proteins
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1579813/full
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