Strategy for improving L-isoleucine production efficiency in Corynebacterium glutamicum
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As one of the three branched-chain amino acids essential for human body, L-isoleucine is widely used in food, medicine, and feed industries. At present, L-isoleucine is mainly produced by microbial fermentation, and the main production strain is Corynebacterium glutamicum. The biosynthetic pathway of L-isoleucine in C. glutamicum is complex, and the activity of key enzymes and the transcription of key genes in the pathway are strictly regulated. The intracellularly synthesized L-isoleucine is secreted by transporters, and the activity of the transporters is also regulated. These intricate regulatory mechanisms increase the difficulty to engineer the L-isoleucine-producing C. glutamicum. This article focuses on the mechanism of L-isoleucine biosynthesis, secretion, and regulation in C. glutamicum and reviews the various metabolic engineering strategies for improving L-isoleucine production efficiency in C. glutamicum.
KeywordsCorynebacterium glutamicum L-Isoleucine Metabolic engineering Branched-chain amino acids Microbial fermentation L-Isoleucine biosynthesis Metabolic regulation Strain development
This work was supported by the National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-10), and the Collaborative Innovation Center of Jiangsu Modern Industrial Fermentation.
Compliance with ethical standards
This article does not contain any studies with human or animal subject.
Conflict of interest
The author declares that he has no conflict of interest.
- Becker J, Gießelmann G, Hoffmann SL, Wittmann C (2018) Corynebacterium glutamicum for sustainable bioproduction: from metabolic physiology to systems metabolic engineering. Adv Biochem Eng Biotechnol 162:217–263Google Scholar
- Colón GE, Jetten MS, Nguyen TT, Gubler ME, Follettie MT, Sinskey AJ, Stephanopoulos G (1995) Effect of inducible thrB expression on amino acid production in Corynebacterium lactofermentum ATCC 21799. Appl Environ Microbiol 61:74–78Google Scholar
- Guillouet S, Rodal AA, An G, Lessard PA, Sinskey AJ (1999) Expression of the Escherichia coli catabolic threonine dehydratase in Corynebacterium glutamicum and its effect on isoleucine production. Appl Environ Microbiol 65(7):3100–3107Google Scholar
- Kelle R, Hermann T, Weuster-Botz D, Eggeling L, Krämer R, Wandrey C (1996) Glucose-controlled L-isoleucine fed-batch production with recombinant strains of Corynebacterium glutamicum. J Biotechnol 50:123–136Google Scholar
- Möckel B, Eggeling L, Sahm H (1994) Threonine dehydratases of Corynebacterium glutamicum with altered allosteric control: their generation and biochemical and structural analysis. Mol Microbiol 13:833–842Google Scholar
- Morbach S, Sahm H, Eggeling L (1995) Use of feedback-resistant threonine dehydratases of Corynebacterium glutamicum to increase carbon flux towards L-isoleucine. Appl Environ Microbiol 61:4315–4320Google Scholar
- Morbach S, Sahm H, Eggeling L (1996b) L-Isoleucine production with Corynebacterium glutamicum: further flux increase and limitation of export. Appl Environ Microbiol 62:4345–4351Google Scholar
- Nie C, He T, Zhang W, Zhang G, Ma X (2018) Branched chain amino acids: beyond nutrition metabolism. Int J Mol Sci, 19(4): E954Google Scholar
- Plassmeier JK, Busche T, Molck S, Persicke M, Pühler A, Rückert C, Kalinowski J (2013) A propionate-inducible expression system based on the Corynebacterium glutamicum prpD2 promoter and PrpR activator and its application for the redirection of amino acid biosynthesis pathways. J Biotechnol 163:225–232CrossRefGoogle Scholar
- Sun JK, Wu XJ, Shi JM, Xu QY, Xie XX, Chen N (2012) Effect of pH on the process of Escherichia coli L-isoleucine fermentation. Food Ferment Ind 38:12–16Google Scholar
- Vogt M, Krumbach K, Bang WG, van Ooyen J, Noack S, Klein B, Bott M, Eggeling L (2015) The contest for precursors: channelling L-isoleucine synthesis in Corynebacterium glutamicum without byproduct formation. Appl Microbiol Biotechnol 99:791–800Google Scholar
- Yamamoto K, Tsuchisaka A, Yukawa H (2017) Branched-chain amino acids. Adv Biochem Eng Biotechnol 159:103–128Google Scholar
- Yin L, Hu X, Wang X (2014a) Proteomic analysis of L-isoleucine production by Corynebacterium glutamicum. J Pure Appl Microbiol 8:899–908Google Scholar