vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-22-90vavilov-3575Research ArticleСИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯSYSTEMS COMPUTATIONAL BIOLOGYРациональная метаболическая инженерия Corynebacterium glutamicum для продукции L-валинаRational metabolic engineering of Corynebacterium glutamicum to create a producer of L-valineШереметьеваМ. Е.SheremetievaM. E.

Москва

Moscow

m.e.sheremetieva@gmail.comАнуфриевК. Э.AnufrievK. E.

Москва

Moscow

ХлебодароваТ. М.KhlebodarovaT. M.

Новосибирск

Novosibirsk

КолчановН. А.KolchanovN. A.

Новосибирск

Novosibirsk

ЯненкоА. С.YanenkoA. S.

Москва

Moscow

Национальный исследовательский центр «Курчатовский институт», Курчатовский геномный центрРоссияNRC “Kurchatov Institute”, Kurchatov Genomic CenterRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Курчатовский геномный центр ИЦиГ СО РАНРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASRussian Federation202204012023268743757Copyright © Шереметьева М.Е., Ануфриев К.Э., Хлебодарова Т.М., Колчанов Н.А., Яненко А.С., 20232023Шереметьева М.Е., Ануфриев К.Э., Хлебодарова Т.М., Колчанов Н.А., Яненко А.С.Sheremetieva M.E., Anufriev K.E., Khlebodarova T.M., Kolchanov N.A., Yanenko A.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3575

L-Валин – одна из девяти аминокислот, которые не могут быть синтезированы de novo высшими организмами и должны поступать с пищей. Эта аминокислота не только служит строительным материалом для белков, но также регулирует белковый и энергетический обмен и участвует в нейротрансмиссии. L-Валин используется в пищевой и фармацевтической промышленности, медицине и косметике, но в первую очередь в качестве кормовой добавки для животных. Добавление L-валина в корм отдельно или в смеси с другими незаменимыми аминокислотами позволяет использовать корма с меньшим содержанием сырого белка, повышает качество и количество мяса свиней и цыплят-бройлеров, а также улучшает репродуктивные функции сельскохозяйственных животных. Несмотря на то что рынок L-валина постоянно растет, в нашей стране эта аминокислота пока не производится. В современных условиях создание штаммов-продуцентов и организация производства L-валина для России особенно актуальны. Один из наиболее часто используемых базовых микроорганизмов для создания продуцентов аминокислот наряду с Escherichia coli – почвенная бактерия Corynebacterium glutamicum. Обзор посвящен анализу основных стратегий разработки продуцентов L-валина на базе C. glutamicum. Рассмотрены различные аспекты биосинтеза L-валина у коринебактерий: биохимия, стехиометрия и регуляция процесса, ферменты и соответствующие им гены, системы экспорта и импорта, связь биосинтеза L-валина с центральным метаболизмом клетки. Выявлены ключевые генетические элементы для создания штаммов-продуцентов на основе C. glutamicum. Описано использование метаболической инженерии для усиления реакций биосинтеза L-валина и уменьшения образования побочных продуктов. Показаны перспективы усовершенствования штаммов с точки зрения повышения их продуктивности и улучшения технологических характеристик. Информация, представленная в обзоре, может быть использована при получении продуцентов других аминокислот с разветв ленной боковой цепью – L-лейцина и L-изолейцина, а также D-пантотената.

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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The authors declare that there are no conflicts of interest present.