Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine

L-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the fo...

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Main Authors: M. E. Sheremetieva, K. E. Anufriev, T. M. Khlebodarova, N. A. Kolchanov, A. S. Yanenko
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2023-01-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/3575
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author M. E. Sheremetieva
K. E. Anufriev
T. M. Khlebodarova
N. A. Kolchanov
A. S. Yanenko
author_facet M. E. Sheremetieva
K. E. Anufriev
T. M. Khlebodarova
N. A. Kolchanov
A. S. Yanenko
author_sort M. E. Sheremetieva
collection DOAJ
description L-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the food and pharmaceutical industries, medicine and cosmetics, but primarily as an animal feed additive. Adding L-valine to feed, alone or mixed with other essential amino acids, allows for feeds with lower crude protein content, increases the quality and quantity of pig meat and broiler chicken meat, as well as improves reproductive functions of farm animals. Despite the fact that the market for L-valine is constantly growing, this amino acid is not yet produced in our country. In modern conditions, the creation of strains-producers and organization of L-valine production are especially relevant for Russia. One of the basic microorganisms most commonly used for the creation of amino acid producers, along with Escherichia coli, is the soil bacterium Corynebacterium glutamicum. This review is devoted to the analysis of the main strategies for the development of L- valine producers based on C. glutamicum. Various aspects of L-valine biosynthesis in C. glutamicum are reviewed: process biochemistry, stoichiometry and regulation, enzymes and their corresponding genes, export and import systems, and the relationship of L-valine biosynthesis with central cell metabolism. Key genetic elements for the creation of C. glutamicum-based strains-producers are identified. The use of metabolic engineering to enhance L-valine biosynthesis reactions and to reduce the formation of byproducts is described. The prospects for improving strains in terms of their productivity and technological characteristics are shown. The information presented in the review can be used in the production of producers of other amino acids with a branched side chain, namely L-leucine and L-isoleucine, as well as D-pantothenate.
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publishDate 2023-01-01
publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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series Вавиловский журнал генетики и селекции
spelling doaj-art-c9306c9d2c6b452bb456dd82c473f7c42025-02-01T09:58:11ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-01-0126874375710.18699/VJGB-22-901312Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valineM. E. Sheremetieva0K. E. Anufriev1T. M. Khlebodarova2N. A. Kolchanov3A. S. Yanenko4NRC “Kurchatov Institute”, Kurchatov Genomic CenterNRC “Kurchatov Institute”, Kurchatov Genomic CenterInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASNRC “Kurchatov Institute”, Kurchatov Genomic CenterL-Valine is one of the nine amino acids that cannot be synthesized de novo by higher organisms and must come from food. This amino acid not only serves as a building block for proteins, but also regulates protein and energy metabolism and participates in neurotransmission. L-Valine is used in the food and pharmaceutical industries, medicine and cosmetics, but primarily as an animal feed additive. Adding L-valine to feed, alone or mixed with other essential amino acids, allows for feeds with lower crude protein content, increases the quality and quantity of pig meat and broiler chicken meat, as well as improves reproductive functions of farm animals. Despite the fact that the market for L-valine is constantly growing, this amino acid is not yet produced in our country. In modern conditions, the creation of strains-producers and organization of L-valine production are especially relevant for Russia. One of the basic microorganisms most commonly used for the creation of amino acid producers, along with Escherichia coli, is the soil bacterium Corynebacterium glutamicum. This review is devoted to the analysis of the main strategies for the development of L- valine producers based on C. glutamicum. Various aspects of L-valine biosynthesis in C. glutamicum are reviewed: process biochemistry, stoichiometry and regulation, enzymes and their corresponding genes, export and import systems, and the relationship of L-valine biosynthesis with central cell metabolism. Key genetic elements for the creation of C. glutamicum-based strains-producers are identified. The use of metabolic engineering to enhance L-valine biosynthesis reactions and to reduce the formation of byproducts is described. The prospects for improving strains in terms of their productivity and technological characteristics are shown. The information presented in the review can be used in the production of producers of other amino acids with a branched side chain, namely L-leucine and L-isoleucine, as well as D-pantothenate.https://vavilov.elpub.ru/jour/article/view/3575<i>corynebacterium glutamicum</i>l-valinemetabolic engineeringproducer strain
spellingShingle M. E. Sheremetieva
K. E. Anufriev
T. M. Khlebodarova
N. A. Kolchanov
A. S. Yanenko
Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
Вавиловский журнал генетики и селекции
<i>corynebacterium glutamicum</i>
l-valine
metabolic engineering
producer strain
title Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
title_full Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
title_fullStr Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
title_full_unstemmed Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
title_short Rational metabolic engineering of <i>Corynebacterium glutamicum</i> to create a producer of L-valine
title_sort rational metabolic engineering of i corynebacterium glutamicum i to create a producer of l valine
topic <i>corynebacterium glutamicum</i>
l-valine
metabolic engineering
producer strain
url https://vavilov.elpub.ru/jour/article/view/3575
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AT keanufriev rationalmetabolicengineeringoficorynebacteriumglutamicumitocreateaproduceroflvaline
AT tmkhlebodarova rationalmetabolicengineeringoficorynebacteriumglutamicumitocreateaproduceroflvaline
AT nakolchanov rationalmetabolicengineeringoficorynebacteriumglutamicumitocreateaproduceroflvaline
AT asyanenko rationalmetabolicengineeringoficorynebacteriumglutamicumitocreateaproduceroflvaline