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Strategy for improving L-isoleucine production efficiency in Corynebacterium glutamicum

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Abstract

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.

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References

  • Abatemarco J, Hill A, Alper HS (2013) Expanding the metabolic engineering toolbox with directed evolution. Biotechnol J 8:1397–1410

    Article  CAS  PubMed  Google Scholar 

  • 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 162:217–263

    PubMed  Google Scholar 

  • Chae TU, Choi SY, Kim JW, Ko YS, Lee SY (2017) Recent advances in systems metabolic engineering tools and strategies. Curr Opin Biotechnol 47:67–82

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Meyer W, Rappert S, Sun J, Zeng AP (2011) Coevolutionary analysis enabled rational deregulation of allosteric enzyme inhibition in Corynebacterium glutamicum for lysine production. Appl Environ Microbiol 77:4352–4360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen C, Li Y, Hu J, Dong X, Wang X (2015) Metabolic engineering of Corynebacterium glutamicum ATCC13869 for l-valine production. Metab Eng 29:66–75

    Article  CAS  PubMed  Google 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 61:74–78

    PubMed  PubMed Central  Google Scholar 

  • Dong X, Quinn PJ, Wang X (2011) Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of L-threonine. Biotechnol Adv 29:11–23

    Article  CAS  PubMed  Google Scholar 

  • Dong X, Quinn PJ, Wang X (2012) Microbial metabolic engineering for L-threonine production. Subcell Biochem 64:283–302

    Article  CAS  PubMed  Google Scholar 

  • Dong X, Zhao Y, Hu J, Li Y, Wang X (2016a) Attenuating l-lysine production by deletion of ddh and lysE and their effect on l-threonine and l-isoleucine production in Corynebacterium glutamicum. Enzym Microb Technol 93-94:70–78

    Article  CAS  Google Scholar 

  • Dong X, Zhao Y, Zhao J, Wang X (2016b) Characterization of aspartate kinase and homoserine dehydrogenase from Corynebacterium glutamicum IWJ001 and systematic investigation of L-isoleucine biosynthesis. J Ind Microbiol Biotechnol 43:873–885

    Article  CAS  PubMed  Google Scholar 

  • Elisáková V, Pátek M, Holátko J, Nesvera J, Leyval D, Goergen JL, Delaunay S (2005) Feedback-resistant acetohydroxy acid synthase increases valine production in Corynebacterium glutamicum. Appl Environ Microbiol 71:207–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Follettie MT, Shin HK, Sinskey AJ (1988) Organization and regulation of the Corynebacterium glutamicum hom-thrB and thrC loci. Mol Microbiol 2:53–62

    Article  CAS  PubMed  Google Scholar 

  • Goldbeck O, Seibold GM (2018) Construction of pOGOduet - An inducible, bicistronic vector for synthesis of recombinant proteins in Corynebacterium glutamicum. Plasmid 95:11–15

    Article  CAS  PubMed  Google 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):3100–3107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guillouet S, Rodal AA, An GH, Gorret N, Lessard PA, Sinskey AJ (2001) Metabolic redirection of carbon flow toward isoleucine by expressing a catabolic threonine dehydratase in a threonine-overproducing Corynebacterium glutamicum. Appl Microbiol Biotechnol 57(5–6):667–673

    Article  CAS  PubMed  Google Scholar 

  • Guo Y, Han M, Xu J, Zhang W (2015a) Analysis of acetohydroxyacid synthase variants from branched-chain amino acids-producing strains and their effects on the synthesis of branched-chain amino acids in Corynebacterium glutamicum. Protein Expr Purif 109:106–112

    Article  CAS  PubMed  Google Scholar 

  • Guo Y, Xu J, Han M, Zhang W (2015b) Generation of mutant threonine dehydratase and its effects on isoleucine synthesis in Corynebacterium glutamicum. World J Microbiol Biotechnol 31:1369–1377

    Article  CAS  PubMed  Google Scholar 

  • Hashiguchi K, Kojima H, Sato K, Sano K (1997) Effects of an Escherichia coli ilvA mutant gene encoding feedback-resistant threonine deaminase on L-isoleucine production by Brevibacterium flavum. Biosci Biotechnol Biochem 61:105–108

    Article  CAS  PubMed  Google Scholar 

  • Holátko J, Elisáková V, Prouza M, Sobotka M, Nesvera J, Pátek M (2009) Metabolic engineering of the L-valine biosynthesis pathway in Corynebacterium glutamicum using promoter activity modulation. J Biotechnol 139(3):203–210

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Tan Y, Li Y, Hu X, Xu D, Wang X (2013) Construction and application of an efficient multiple-gene-deletion system in Corynebacterium glutamicum. Plasmid 70:303–313

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Li Y, Zhang H, Tan Y, Wang X (2014) Construction of a novel expression system for use in Corynebacterium glutamicum. Plasmid 75:18–26

    Article  CAS  PubMed  Google Scholar 

  • Kalinowski J, Cremer J, Bachmann B, Eggeling L, Sahm H, Pühler A (1991) Genetic and biochemical analysis of the aspartokinase from Corynebacterium glutamicum. Mol Microbiol 5:1197–1204

    Article  CAS  PubMed  Google Scholar 

  • Kang MK, Lee J, Um Y, Lee TS, Bott M, Park SJ, Woo HM (2014) Synthetic biology platform of CoryneBrick vectors for gene expression in Corynebacterium glutamicum and its application to xylose utilization. Appl Microbiol Biotechnol 98:5991–6002

    Article  CAS  PubMed  Google Scholar 

  • Keilhauer C, Eggeling L, Sahm H (1993) Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon. J Bacteriol 175:5595–5603

    Article  CAS  PubMed  PubMed Central  Google 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 50:123–136

  • Kennerknecht N, Sahm H, Yen MR, Pátek M, Saier MH Jr, Eggeling L (2002) Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded membe of a new translocator family. J Bacteriol 184:3947–3956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kortmann M, Kuhl V, Klaffl S, Bott M (2015) A chromosomally encoded T7 RNA polymerase-dependent gene expression system for Corynebacterium glutamicum: construction and comparative evaluation at the single-cell level. Microb Biotechnol 8:253–265

    Article  CAS  Google Scholar 

  • Krömer JO, Heinzle E, Schröder H, Wittmann C (2006) Accumulation of homolanthionine and activation of a novel pathway for isoleucine biosynthesis in Corynebacterium glutamicum McbR deletion strains. J Bacteriol 188(2):609–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lange C, Mustafi N, Frunzke J, Kennerknecht N, Wessel M, Bott M, Wendisch VF (2012) Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for l-methionine and branched-chain amino acids. J Biotechnol 158:231–241

    Article  CAS  PubMed  Google Scholar 

  • Lausberg F, Chattopadhyay AR, Heyer A, Eggeling L, Freudl R (2012) A tetracycline inducible expression vector for Corynebacterium glutamicum allowing tightly regulable gene expression. Plasmid 68:142–147

    Article  CAS  PubMed  Google Scholar 

  • Lee J (2014) Development and characterization of expression vectors for Corynebacterium glutamicum. J Microbiol Biotechnol 24:70–79

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Wei H, Wang T, Xu Q, Zhang C, Fan X, Ma Q, Chen N, Xie X (2017) Current status on metabolic engineering for the production of l-aspartate family amino acids and derivatives. Bioresour Technol 245:1588–1602

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Wang Y, Lu Y, Zheng P, Sun J, Ma Y (2017) Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum. Microb Cell Factories 16:205

    Article  CAS  Google Scholar 

  • Ma W, Wang J, Li Y, Hu X, Shi F, Wang X (2016) Enhancing pentose phosphate pathway in Corynebacterium glutamicum to improve L-isoleucine production. Biotechnol Appl Biochem 63:877–885

    Article  CAS  PubMed  Google Scholar 

  • Ma W, Wang J, Li Y, Yin L, Wang X (2018) Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) co-produced with L-isoleucine in Corynebacterium glutamicum WM001. Microb Cell Factories 17:93

    Article  CAS  Google Scholar 

  • Mateos LM, Pisabarro A, Pátek M, Malumbres M, Guerrero C, Eikmanns BJ, Sahm H, Martín JF (1994) Transcriptional analysis and regulatory signals of the hom-thrB cluster of Brevibacterium lactofermentum. J Bacteriol 176:7362–7371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McHardy AC, Tauch A, Ruckert C, Pühler A, Kalinowski J (2003) Genome-based analysis of biosynthetic aminotransferase genes of Corynebacterium glutamicum. J Biotechnol 104:229–240

    Article  CAS  PubMed  Google Scholar 

  • Mei J, Xu N, Ye C, Liu L, Wu J (2016) Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114. Gene 575:615–622

    Article  CAS  PubMed  Google Scholar 

  • Miyajima R, Shiio I (1970) Regulation of aspartate family amino acid biosynthesis in Brevibacterium flavum. III Properties of homoserine dehydrogenase. J Biochem 68:311–319

    Article  CAS  PubMed  Google 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 13:833–842

  • 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 61:4315–4320

  • Morbach S, Kelle R, Winkels S, Sahm H, Eggeling L (1996a) Engineering the homoserine dehydrogenase and threonine dehydratase control points to analyse flux towards L-isoleucine in Corynebacterium glutamicum. Appl Microbiol Biotechnol 45:612–620

    Article  CAS  Google Scholar 

  • Morbach S, Sahm H, Eggeling L (1996b) L-Isoleucine production with Corynebacterium glutamicum: further flux increase and limitation of export. Appl Environ Microbiol 62:4345–4351

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morbach S, Junger C, Sahm H, Eggeling L (2000) Attenuation control of ilvBNC in Corynebacterium glutamicum: evidence of leader peptide formation without the presence of a ribosome binding site. J Biosci Bioeng 90:501–507

    Article  CAS  PubMed  Google Scholar 

  • Mustafi N, Grünberger A, Kohlheyer D, Bott M, Frunzke J (2012) The development and application of a single-cell biosensor for the detection of l-methionine and branched-chain amino acids. Metab Eng 14(4):449–457

    Article  CAS  PubMed  Google Scholar 

  • Nešvera J, Pátek M (2011) Tools for genetic manipulations in Corynebacterium glutamicum and their applications. Appl Microbiol Biotechnol 90:1641–1654

    Article  CAS  PubMed  Google 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): E954

  • Okibe N, Suzuki N, Inui M, Yukawa H (2011) Efficient markerless gene replacement in Corynebacterium glutamicum using a new temperature-sensitive plasmid. J Microbiol Methods 85:155–163

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Lee SY (2010a) Fermentative production of branched chain amino acids: a focus on metabolic engineering. Appl Microbiol Biotechnol 85:491–506

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Lee SY (2010b) Metabolic pathways and fermentative production of L-aspartate family amino acids. Biotechnol J 5:560–577

    Article  CAS  PubMed  Google Scholar 

  • Peng F, Wang X, Sun Y, Dong G, Yang Y, Liu X, Bai Z (2017) Efficient gene editing in Corynebacterium glutamicum using the CRISPR/Cas9 system. Microb Cell Factories 16(1):201

    Article  CAS  Google Scholar 

  • Petit C, Kim Y, Lee SK, Brown J, Larsen E, Ronning DR, Suh JW, Kang CM (2018) Reduction of feedback inhibition in homoserine kinase (ThrB) of Corynebacterium glutamicum enhances l-threonine biosynthesis. ACS Omega 3:1178–1186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfeifer E, Gätgens C, Polen T, Frunzke J (2017) Adaptive laboratory evolution of Corynebacterium glutamicum towards higher growth rates on glucose minimal medium. Sci Rep 7:16780

    Article  CAS  PubMed  PubMed Central  Google 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 163:225–232

    Article  CAS  PubMed  Google Scholar 

  • Reed KB, Alper HS (2017) Expanding beyond canonical metabolism: interfacing alternative elements, synthetic biology, and metabolic engineering. Synth Syst Biotechnol 3:20–33

    Article  PubMed  PubMed Central  Google Scholar 

  • Reinscheid DJ, Eikmanns BJ, Sahm H (1991) Analysis of a Corynebacterium glutamicum hom gene coding for a feedback-resistant homoserine dehydrogenase. J Bacteriol 173:3228–3230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen J, Chen J, Jensen PR, Solem C (2017) A novel genetic tool for metabolic optimization of Corynebacterium glutamicum: efficient and repetitive chromosomal integration of synthetic promoter-driven expression libraries. Appl Microbiol Biotechnol 101:4737–4746

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Huan X, Wang X, Ning J (2012) Overexpression of NAD kinases improves the L-isoleucine biosynthesis in Corynebacterium glutamicum ssp. lactofermentum. Enzym Microb Technol 51(2):73–80

    Article  CAS  Google Scholar 

  • Shi F, Li K, Huan X, Wang X (2013) Expression of NAD(H) kinase and glucose-6-phosphate dehydrogenase improve NADPH supply and L-isoleucine biosynthesis in Corynebacterium glutamicum ssp. lactofermentum. Appl Biochem Biotechnol 171:504–521

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Li K, Li Y (2015a) Comparative proteome analysis of global effect of POS5 and zwf-ppnK overexpression in L-isoleucine producing Corynebacterium glutamicum ssp. lactofermentum. Biotechnol Lett 37:1063–1071

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Niu T, Fang H (2015b) 4-Hydroxyisoleucine production of recombinant Corynebacterium glutamicum ssp. lactofermentum under optimal corn steep liquor limitation. Appl Microbiol Biotechnol 99:3851–3863

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Fang H, Niu T, Lu Z (2016) Overexpression of ppc and lysC to improve the production of 4-hydroxyisoleucine and its precursor l-isoleucine in recombinant Corynebacterium glutamicum ssp. lactofermentum. Enzym Microb Technol 87-88:79–85

    Article  CAS  Google Scholar 

  • Shi F, Zhang M, Li Y, Fang H (2018) Sufficient NADPH supply and pknG deletion improve 4-hydroxyisoleucine production in recombinant Corynebacterium glutamicum. Enzym Microb Technol 115:1–8

    Article  CAS  Google Scholar 

  • Stephanopoulos GN, Uallino JJ (1991) Network rigidity and metabolic engineering in metabolite production. Science 252:1675–1681

    Article  CAS  PubMed  Google 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 38:12–16

    CAS  Google Scholar 

  • Tan Y, Xu D, Li Y, Wang X (2012) Construction of a novel sacB-based system for marker-free gene deletion in Corynebacterium glutamicum. Plasmid 67:44–52

    Article  CAS  PubMed  Google Scholar 

  • Tauch A, Hermann T, Burkovski A, Krämer R, Pühler A, Kalinowski J (1998) Isoleucine uptake in Corynebacterium glutamicum ATCC 13032 is directed by the brnQ gene product. Arch Microbiol 169:303–312

    Article  CAS  PubMed  Google Scholar 

  • Vogt M, Haas S, Klaffl S, Polen T, Eggeling L, van Ooyen J, Bott M (2014) Pushing product formation to its limit: metabolic engineering of Corynebacterium glutamicum for L-leucine overproduction. Metab Eng 22:40–52

    Article  CAS  PubMed  Google 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 99:791–800

  • Wang J, Wen B, Wang J, Xu Q, Zhang C, Chen N, Xie X (2013) Enhancing (L)-isoleucine production by thrABC overexpression combined with alaT deletion in Corynebacterium glutamicum. Appl Biochem Biotechnol 171:20–30

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Quinn PJ, Yan A (2015a) Kdo2 -lipid A: structural diversity and impact on immunopharmacology. Biol Rev Camb Philos Soc 90:408–427

    Article  PubMed  Google Scholar 

  • Wang J, Wen B, Xu Q, Xie X, Chen N (2015b) Optimization of carbon source and glucose feeding strategy for improvement of L-isoleucine production by Escherichia coli. Biotechnol Biotechnol Equip 29:374–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Zhang H, Quinn PJ (2018) Production of L-valine from metabolically engineered Corynebacterium glutamicum. Appl Microbiol Biotechnol 102:4319–4330

    Article  CAS  PubMed  Google Scholar 

  • Wendisch VF (2014) Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development. Curr Opin Biotechnol 30:51–58

    Article  CAS  PubMed  Google Scholar 

  • Woo HM, Park JB (2014) Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum. J Biotechnol 180:43–51

    Article  CAS  PubMed  Google Scholar 

  • Xie X, Xu L, Shi J, Xu Q, Chen N (2012) Effect of transport proteins on L-isoleucine production with the L-isoleucine-producing strain Corynebacterium glutamicum YILW. J Ind Microbiol Biotechnol 39(10):1549–1556

    Article  CAS  PubMed  Google Scholar 

  • Xu D, Tan Y, Huan X, Hu X, Wang X (2010a) Construction of a novel shuttle vector for use in Brevibacterium flavum, an industrial amino acid producer. J Microbiol Methods 80:86–92

    Article  CAS  PubMed  Google Scholar 

  • Xu D, Tan Y, Shi F, Wang X (2010b) An improved shuttle vector constructed for metabolic engineering research in Corynebacterium glutamicum. Plasmid 64:85–91

    Article  CAS  PubMed  Google Scholar 

  • Xu D, Tan Y, Li Y, Wang X (2011) Construction of a novel promoter-probe vector and its application for screening strong promoter for Brevibacterium flavum metabolic engineering. World J Microbiol Biotechnol 27:961–968

    Article  CAS  Google Scholar 

  • Yamamoto K, Tsuchisaka A, Yukawa H (2017) Branched-chain amino acids. Adv Biochem Eng Biotechnol 159:103–128

    CAS  PubMed  Google Scholar 

  • Yang J, Yang S (2017) Comparative analysis of Corynebacterium glutamicum genomes: a new perspective for the industrial production of amino acids. BMC Genomics 18:940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin L, Hu X, Xu D, Ning J, Chen J, Wang X (2012) Co-expression of feedback-resistant threonine dehydratase and acetohydroxy acid synthase increase L-isoleucine production in Corynebacterium glutamicum. Metab Eng 14(5):542–550

    Article  CAS  PubMed  Google Scholar 

  • Yin L, Shi F, Hu X, Chen C, Wang X (2013) Increasing l-isoleucine production in Corynebacterium glutamicum by overexpressing global regulator Lrp and two-component export system BrnFE. J Appl Microbiol 114:1369–1377

    Article  CAS  PubMed  Google Scholar 

  • Yin L, Hu X, Wang X (2014a) Proteomic analysis of L-isoleucine production by Corynebacterium glutamicum. J Pure Appl Microbiol 8:899–908

    CAS  Google Scholar 

  • Yin L, Zhao J, Chen C, Hu X, Wang X (2014b) Enhancing the carbon flux and NADPH supply to increase L-isoleucine production in Corynebacterium glutamicum. Biotechnol Bioprocess Eng 19:132–142

    Article  CAS  Google Scholar 

  • Yoshida A, Tomita T, Kurihara T, Fushinobu S, Kuzuyama T, Nishiyama M (2007) Structural insight into concerted inhibition of alpha 2 beta 2-type aspartate kinase from Corynebacterium glutamicum. J Mol Biol 368:521–536

    Article  CAS  PubMed  Google Scholar 

  • Yoshida A, Tomita T, Kuzuyama T, Nishiyama M (2010) Mechanism of concerted inhibition of alpha2beta2-type hetero-oligomeric aspartate kinase from Corynebacterium glutamicum. J Biol Chem 285:27477–27486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Li Y, Wang X (2013) Molecular evolution of threonine dehydratase in bacteria. PLoS One 8(12):e80750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Li Y, Wang X (2014) The role of ACT-like subdomain in bacterial threonine dehydratases. PLoS One 9(1):e87550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Shang X, Lai S, Zhang G, Liang Y, Wen T (2012) Development and application of an arabinose-inducible expression system by facilitating inducer uptake in Corynebacterium glutamicum. Appl Environ Microbiol 78:5831–5838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Jia H, Xu D (2015) Construction of a novel twin-arginine translocation (Tat)-dependent type expression vector for secretory production of heterologous proteins in Corynebacterium glutamicum. Plasmid 82:50–55

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Li Y, Wang C, Wang X (2018) Understanding the high L-valine production in Corynebacterium glutamicum VWB-1 using transcriptomics and proteomics. Sci Rep 8:3632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Hu X, Li Y, Wang X (2015) Overexpression of ribosome elongation factor G and recycling factor increases L-isoleucine production in Corynebacterium glutamicum. Appl Microbiol Biotechnol 99:4795–4805

    Article  CAS  PubMed  Google Scholar 

  • Zheng B, Ma X, Wang N, Ding T, Guo L, Zhang X, Yang Y, Li C, Huo YX (2018) Utilization of rare codon-rich markers for screening amino acid overproducers. Nat Commun 9:3616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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.

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Wang, X. Strategy for improving L-isoleucine production efficiency in Corynebacterium glutamicum. Appl Microbiol Biotechnol 103, 2101–2111 (2019). https://doi.org/10.1007/s00253-019-09632-2

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