Skip to main content
SpringerLink
Log in

Metabolic Engineering of Lysine Producing Corynebacterium glutamicum Strains

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

The review is devoted to the analysis of the current achievements of Corynebacterium glutamicum metabolic engineering for the production of lysine. Key genes of lysine biosynthesis in C. glutamicum and ways of creating new genetically modified strains are considered. The role of different plasmids, vector cassettes, and promoter types for the regulation of gene expression in C. glutamicum is described. Information is provided on the use of carbon-containing substrates (hexose, pentose, lactic acid, mannitol) for the production of lysine. Possibilities of using CRISPR technology in genetic engineering of C. glutamicum are considered. Genetic changes in C. glutamicum allowed the use of alternative substrates and contributed to the increase of lysine accumulation in the culture fluid. The data that may be used for the creation of new lysine overproduction strains are summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Becker, J. and Wittmann, C., Industrial microorganisms: Corynebacterium glutamicum, in Industrial Biotechnology, Wittmann, C. and Liao, J.C., Eds., Germany, Weinheim, Wiley-VCH, 2017, pp. 183–203. https://doi.org/10.1002/9783527807796.ch6

  2. Andriiash, G.S., Zabolotna, G.M., Bondarenko, V.S., and Shulga, S.M., Gene 16S rRNA sequence phylogenetic analysis of lysine producers, Biotechnol. Acta, 2014, vol. 7, no. 6, pp. 40–45. https://doi.org/10.15407/biotech7.06.040

    Article  Google Scholar 

  3. Tigunova, O.O., Andriiash, G.S., Beyko, N.E., and Shulga, S.M., Phylogenrtic analysis of lysine, threonine and butanolstraine-producers, Fact. Exp. Evol. Org., 2017, vol. 21, pp. 288–292.

    Google Scholar 

  4. Ma, Q., Zhang, Q., Xu, Q., Zhang, C., Li, Y., Fan, X., Xie, X., and Chen, N., Systems metabolicengineering strategies for the production of amino acids, Synth. Syst. Biotechnol., 2017, no. 2, pp. 87–96. https://doi.org/10.1016/j.synbio.2017.07.003

  5. Andriiash, G.S., Zabolotna, G.M., and Shulga, S.M., Regulation and intensification ways of lysine biosynthesis, Microbiol. Biotechnol., 2012, no. 4, pp. 6–17. https://doi.org/10.18524/2307-4663.2012.4(20).90435

  6. Andriiash, G.S., Zabolotna, G.M., Tkachenko, A.F., Blume, Ya.B., and Shulga, S.M., Threonine synthesis of Brevibacterium flavum, in Threonine: Food Sources, Functions and Health Benefits, USA: Nova Publ., 2015, pp. 1–26.

    Google Scholar 

  7. Buschke, N., Schäfer, R., and Becker, J., and Wittmann, C., Metabolic engineering of industrial platform microorganisms for biorefinery applications—optimization of substrate spectrum and process robustness by rational and evolutive strategies, Bioresour. Technol., 2013, vol. 135, pp. 544–554. https://doi.org/10.1016/j.biortech.2012.11.047

  8. Date, M., Itaya, H., Matsui, H., and Kikuchi, Y., Secretion of human epidermal growth factor by Corynebacterium glutamicum,Lett. Appl. Microbiol., 2006, vol. 42, pp. 66–70. https://doi.org/10.1111/j.1472-765X.2005.01802.x

    Article  CAS  PubMed  Google Scholar 

  9. Tryfona, T. and Mak, T., Fermentative production of lysine by Corynebacterium glutamicum: transmembrane transport and metabolic flux analysis, Process Biochem., 2005, vol. 40, pp. 499–508. https://doi.org/10.1016/j.procbio.2004.01.037

    Article  CAS  Google Scholar 

  10. Hermann, T., Industrial production of amino acids by coryneform bacteria, J. Biotechnol., 2003, vol. 104, pp. 155–172. https://doi.org/10.1016/S0168-1656(03)00149-4

    Article  CAS  PubMed  Google Scholar 

  11. Koffas, M.A., Jung, G., Yeol., G., and Stephanopoulos, G., Engineering metabolism and product formation in Corynebacterium glutamicum by coordinated gene overexpression, Metab. Eng., 2003, vol. 5, pp. 32–41. https://doi.org/10.1016/S1096-7176(03)00002-8

    Article  CAS  PubMed  Google Scholar 

  12. Kromer, J.O., Sorgenfrei, O., Klopprogge, K., Heinzle, E., and Wittmann, C., In-depth profiling of lysine-producing Corynebacterium glutamicum by combined analysis of the transcriptome, metabolome, and fluxome, J. Bacteriol., 2004, vol. 186, no. 6, pp. 1769–1784. https://doi.org/10.1128/JB.186.6.1769-1784.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ohnishi, J., Mitsuhashi, S., Hayashi, M., Ando, S., Yokoi, H., Ochiai, K., and Ikeda, M., A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant, Appl. Microbiol. Biotechnol., 2002, vol. 58, pp. 217–223. https://doi.org/10.1007/s00253-001-0883-6

    Article  CAS  PubMed  Google Scholar 

  14. Papagianni, M., Recent advances in engineering the central carbon metabolism of industrially important bacteria, Microb. Cell Factories, 2012, vol. 11, pp. 1–13. https://doi.org/10.1186/1475-2859-11-50

    Article  CAS  Google Scholar 

  15. Sun, Y., Guo, W., Wang, F., Zhan, C., Yang, Y., Liu, X., and Bai, Z., Transcriptome analysis of Corynebacterium glutamicum in the process of recombinant protein expression in bioreactors, PLoS One, 2017, vol. 12, no. 4, pp. 1–18. https://doi.org/10.1371/journal.pone.0174824

    Article  CAS  Google Scholar 

  16. Eikmanns, B.J., Central metabolism: tricarboxylic acid cycle and anaplerotic reactions, in Handbook of Corynebacterium glutamicum, Eggelingand, L. and Bott, M., Eds., Boca Raton, FL: CRC Press, 2005, pp. 241–276.

    Google Scholar 

  17. Baritugo, K.A., Kim, H.T., David, Y., Choi, J.-L., Hong, S.H., and Jeong, K.J., Metabolic engineering of Corynebacterium glutamicum for fermentative production of chemicals in biorefinery, Appl. Microbiol. Biotechnol., 2018, vol. 102, pp. 3915–3937. https://doi.org/10.1007/s00253-018-8896-6

    Article  CAS  PubMed  Google Scholar 

  18. Nakamura, Y., Nishio, Y., Ikeo, K., and Gojobori, T., The genome stability in Corynebacterium species due to lack of the recombinational repair system, Gene, 2003, vol. 317, pp. 149–155. https://doi.org/10.1016/S0378-1119(03)00653-X

    Article  CAS  PubMed  Google Scholar 

  19. Leßmeier, L. and Wendisch, V.F., Identification of two mutations increasing the methanol tolerance of Corynebacterium glutamicum,BMC Microbiol., 2015, vol. 15, no. 216. https://doi.org/10.1186/s12866-015-0558-6

  20. Nesvera, J. and Patek, M., Tools for genetic manipulations in Corynebacterium glutamicum and their applications, Appl. Microbiol. Biotechnol., 2011, vol. 90, no. 5, pp. 1641–1654. https://doi.org/10.1007/s00253-011-3272-9

    Article  CAS  PubMed  Google Scholar 

  21. Liebl, W., Sinskey, A.J., and Schleifer, K.H., Expression, secretion, and processing of staphylococcal nuclease by Corynebacterium glutamicum,J. Bacteriol., 1992, vol. 174, no. 6, pp. 1854–1861. https://doi.org/10.1128/jb.174.6.1854-1861.1992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Eikmanns, B.J., Thum-Schmitz, N., Eggeling, L., Ludtke, K.U., and Sahm, H. Nucleotide sequence,expression and transcriptional analysis of the Corynebacterium glutamicum gltA gene encoding citrate synthase, Microbiology, 1994, vol. 140, no. 8, pp. 1817–1828. https://doi.org/10.1099/13500872-140-8-1817

    Article  CAS  PubMed  Google Scholar 

  23. Jakoby, M., Ngouoto-Nkili, C.E., and Burkovski, A., Construction and application of new Corynebacterium glutamicum vectors, Biotechnol. Techniques, 1999, vol. 13, p. 437. https://doi.org/10.1023/A:1008968419217

    Article  CAS  Google Scholar 

  24. Peters-Wendisch, P.G., Schiel, B., Wendisch, V.F., Katsoulidis, E., Mockel, B., Sahm, H., and Eikmanns, B.J., Pyruvate carboxylase is a major bottleneck for glutamate and lysine production by Corynebacterium glutamicum,J. Mol. Microbiol. Biotechnol., 2001, vol. 3, pp. 295–300.

    CAS  PubMed  Google Scholar 

  25. Yasuda, K., Jojima, T., Suda, M., Okino, S., Inui, M., and Yukawa, H., Analyses of the acetate-producing pathways in Corynebacterium glutamicum under oxygen-deprived conditions, Appl. Microbiol. Biotechnol., 2008, vol. 77, no. 4, pp. 853–860. https://doi.org/10.1007/s00253-007-1199-y

    Article  CAS  Google Scholar 

  26. Sato, H., Orishimo, K., Shirai, T., Hirasawa, T., Nagahisa, K., Shimizu, H., and Wachi, M., Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum,J. Biosci. Bioeng., 2008, vol. 106, no. 1, pp. 51–58. https://doi.org/10.1263/jbb.106.51

    Article  CAS  PubMed  Google Scholar 

  27. Krause, F.S., Blombach, B., and Eikmanns, B.J., Metabolic engineering of Corynebacterium glutamicum for 2-ketoisovalerate production, Appl. Environ. Microbiol., 2010, vol. 76, no. 24, pp. 8053–8061. https://doi.org/10.1128/AEM.01710-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yang, Y.F., Zhang, J.J., Wang, S.H., and Zhou, N.Y., Purification and characterization of the ncgli2923-encoded 3-hydroxybenzoate 6-hydroxylase from Corynebacterium glutamicum,J. Basic Microbiol., 2010, vol. 50, no. 6, pp. 599–604. https://doi.org/10.1002/jobm.201000053

    Article  CAS  PubMed  Google Scholar 

  29. Santamaria, R., Gil, J., Mesas, J., and Martin, J., Characterization of an endogenous plasmid and development of cloning vectors and a transformation system in Brevibacterium lactofermentum,J. Gen. Microbiol., 1984, vol. 130, pp. 2237–2246. https://doi.org/10.1099/00221287-130-9-2237

    Article  CAS  Google Scholar 

  30. Sonnen, H., Thierbach, G., Kautz, S., Kalinowski, J., Schneider, J., Puhler, A., and Kutzner, H.J., Characterization of pGA1, a new plasmid from Corynebacterium glutamicum LP-6, Gene, 1991, vol. 107, no. 1, pp. 69–74. https://doi.org/10.1016/0378-1119(91)90298-P

    Article  CAS  PubMed  Google Scholar 

  31. Ozaki, A., Katsumata, R., Oka, T., and Furuya, A., Functional expression of the genes of Escherichia coli in gram-positive Corynebacterium glutamicum,Mol. Gen. Genet., 1984, vol. 196, no. 1, pp. 175–178. https://doi.org/10.1007/BF00334113

    Article  CAS  PubMed  Google Scholar 

  32. Kirchner, O. and Tauch, A., Tools for genetic engineering in the amino acid-producing bacterium Corynebacterium glutamicum,J. Biotechnol., 2003, vol. 104, pp. 287–299. https://doi.org/10.1016/S0168-1656(03)00148-2

    Article  CAS  PubMed  Google Scholar 

  33. Patek, M., Holatko, J., Busche, B., Kalinowski, J., and Nesvera, J., Corynebacterium glutamicum promoters: a practical approach, Microb. Biotechnol., 2013, vol. 6, no. 2, pp. 103–117.

    Article  Google Scholar 

  34. Studier, F.W. and Moffatt, B.A., Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes, J. Mol. Biol., 1986, vol. 189, no. 1, pp. 113–130. https://doi.org/10.1016/0022-2836(86)90385-2

    Article  CAS  PubMed  Google Scholar 

  35. Kortmann, M., Kuhl, V., Klaffl, S., and Bott, M., A chromosomally encoded T7 RNA polymerase-dependent gene expression system for Corynebacterium glutamicum: construction and comparative evaluation at the single-cell level, Microb. Biotechnol., 2015, vol. 8, no. 2, pp. 253–265. https://doi.org/10.1111/1751-7915.12236

    Article  CAS  PubMed  Google Scholar 

  36. Peters-Wendisch, P.G., Schiel, B., Wendisch, V.F., Katsoulidis, E., Mockel, B., Sahm, H., and Eikmanns, B.J., Pyruvate carboxylase is a major bottleneck for glutamate and lysine production by Corynebacterium glutamicum,J. Mol. Microbiol. Biotechnol., 2001, vol. 3, no. 2, pp. 295–300.

    CAS  PubMed  Google Scholar 

  37. Nakunst, D., Larisch, C., Hüser, A.T., Tauch, A., Puhler, A., and Kalinowski, J., The extracytoplasmic function-type sigma factor SigM of Corynebacterium glutamicum ATCC 13032 is involved in transcription of disulfide stress-related genes, J. Bacteriol., 2007, vol. 189, no. 13, pp. 4696–4707. https://doi.org/10.1128/JB.00382-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ehira, S., Teramoto, H., Inui, M., and Yukawa, H., Regulation of Corynebacterium glutamicum heat shock response by the extracytoplasmic-function sigma factor SigH and transcriptional regulators HspR and HrcA, J. Bacteriol., 2009, vol. 191, no. 9, pp. 2964–2972. https://doi.org/10.1128/JB.00112-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Larisch, C., Nakunst, D., Huser, A.T., Tauch, A., and Kalinowski, J., The alternative sigma factor SigBof Corynebacterium glutamicum modulates global gene expression during transition from exponential growth to stationary phase, BMC Genomics, 2007, vol. 8. https://doi.org/10.1186/1471-2164-8-4

  40. Busche, T., Silar, R., Picmanova, M., Patek, M., and Kalinowski, J., Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum,BMC Genomics, 2012, vol. 13, no. 445. https://doi.org/10.1186/1471-2164-13-445

  41. Zhang, Y., Shang, LaiSh., Zhang, G., Liang, Y., and Wen, T., Development and application of an arabinose-inducible expression system by facilitating inducer uptake in Corynebacterium glutamicum,Appl. Environ. Microbiol., 2012, vol. 78, no. 16, pp. 5831–5838. https://doi.org/10.1128/AEM.01147-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yim, S.S., An S.J., Kang M., Lee J., and Jeong K.J. Isolation of fully synthetic promoters for high-level gene expression in Corynebacterium glutamicum,Biotechnol. Bioeng., 2013, vol. 110, no. 11, pp. 2959–2969. https://doi.org/10.1002/bit.24954

    Article  CAS  PubMed  Google Scholar 

  43. Rytter, J.V., Helmark, S., Chen, J., Lezyk, M.J., Solem, C., and Jensen, P.R., Synthetic promoter libraries for Corynebacterium glutamicum,Appl. Microbiol. Biotechnol., 2014, vol. 98, no. 6, pp. 2617–2623. https://doi.org/10.1007/s00253-013-5481-x

    Article  CAS  PubMed  Google Scholar 

  44. Becker, J., Zelder, O., Hafner, S., Schroder, H., and Wittmann, C., From zero to hero-design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production, Metab. Eng., 2011, vol. 13, no. 2, pp. 159–168. https://doi.org/10.1016/j.ymben.2011.01.003

    Article  CAS  PubMed  Google Scholar 

  45. Ooyen, J., Noack, S., Bott, M., Reth, A., and Eggeling, L., Improved L-lysine production with Corynebacterium glutamicum and systemic insight into citrate synthase flux and activity, Biotechnol. Bioeng., 2012, vol. 109, no. 8, pp. 2070–2081. https://doi.org/10.1002/bit.24486

    Article  CAS  PubMed  Google Scholar 

  46. Hänssler, E., Muller, T., Palumbo, K., Patek, M., Brocker, M., Kramer, R., and Burkovski, A., A game with many players: control of gdh transcription in Corynebacterium glutamicum,J. Biotechnol., 2009, vol. 142, pp. 114–122. https://doi.org/10.1016/j.jbiotec.2009.04.007

    Article  CAS  PubMed  Google Scholar 

  47. Tanaka, Y., Okai, N., Teramoto, H., Inui, M., and Yukawa, H., Regulation of the expression of phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) genes in Corynebacterium glutamicum R, Microbiology, 2008, vol. 154, pp. 264–274. https://doi.org/10.1099/mic.0.2007/008862-0

    Article  CAS  PubMed  Google Scholar 

  48. Gaigalat, L., Schluter, J.P., Hartmann, M., Mormann, Tauch, A., Puhler, A., and Kalinowski, J., The DeoR-type transcriptional regulator SugR acts as a repressor for genes encoding the phosphoenol pyruvate: sugar phosphotransferase system (PTS) in Corynebacterium glutamicum, BMC Mol. Biol., 2007, vol. 8. https://doi.org/10.1186/1471-2199-8-104

  49. Ikeda, M., Ohnishi, J., Hayashi, M., and Mitsuhashi, S., A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production, J. Ind. Microbiol. Biotechnol., 2006, vol. 33, pp. 610–615. https://doi.org/10.1007/s10295-006-0104-5

    Article  CAS  PubMed  Google Scholar 

  50. Hayashi, M., Ohnishi, J., Mitsuhashi, S., Yonetani, Y., Hashimoto, S., and Ikeda, M., Transcriptome analysis reveals global expression changes in an industrial l-lysine producer of Corynebacterium glutamicum,Biosci. Biotechnol. Biochem., 2006, vol. 70, pp. 546–550. https://doi.org/10.1271/bbb.70.546

    Article  CAS  PubMed  Google Scholar 

  51. Brinkrolf, K., Schröder, J., Pühler, A., and Tauch, A., The transcriptional regulatory repertoire of Corynebacterium glutamicum: reconstruction of the network controlling pathways involved in lysine and glutamate production, J. Biotech., vol. 149, no. 3, pp. 173–182. https://doi.org/10.1016/j.jbiotec.2009.12.004

  52. Binder, B., Siedler, S., Marienhagen, J., Bott, M., and Eggeling, L., Recombineering in Corynebacterium glutamicum combined with optical nanosensors: a general strategy for fast producer strain generation, Nucleic Acids Res., 2013, vol. 41, no. 12, pp. 6360–6369. https://doi.org/10.1093/nar/gkt312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kortmann, M., Mack, C., Baumgar, M., and Bott, M., Pyruvate carboxylase variants enabling improved lysine production from glucose identified by biosensor-based high-throughput fluorescence-activated cell sorting screening, ACS Synth. Biol., 2019, vol. 8, no. 2, pp. 274–281. https://doi.org/10.1021/acssynbio.8b00510

    Article  CAS  PubMed  Google Scholar 

  54. Wendisch, V.F., Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development, Curr. Opin. Biotechnol., 2014, vol. 30, pp. 51–58. https://doi.org/10.1016/j.copbio.2014.05.004

    Article  CAS  PubMed  Google Scholar 

  55. Chen, Z., Rappert, S., and Zeng, A.P., Rational design of allosteric regulation of homoserine dehydrogenase by a non-natural inhibitor L-lysine, ACS Synth. Biol., 2015, vol. 4, no. 2, pp. 126–131. https://doi.org/10.1021/sb400133g

    Article  CAS  PubMed  Google Scholar 

  56. Zhou, L.B. and Zeng, A.P., Exploring lysine riboswitch for metabolic flux control and improvement of L-lysine synthesis in Corynebacterium glutamicum,ACS Synth. Biol., 2015, no. 4, pp. 729–734. https://doi.org/10.1021/sb500332c

  57. Hoffmann, S.L., Jungmann, L., Schiefelbein, S., Peyriga, L., Cahoreau, E., Portais, J.C., Becker, J., and Wittmann, C., Lysine production from the sugar alcohol mannitol: design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes, Metab. Eng. 2018, vol. 47, pp. 475–487. https://doi.org/10.1016/j.ymben.2018.04.019

    Article  CAS  PubMed  Google Scholar 

  58. Schneider, J., Niermann, K., and Wendisch, V.F., Production of the amino acids L-glutamate, L-lysine, L-ornithine and L-arginine from arabinose by recombinant Corynebacterium glutamicum,J. Biotechnol., 2011, vol. 154, nos. 2–3, pp. 191–198. https://doi.org/10.1016/j.jbiotec.2010.07.009

    Article  CAS  PubMed  Google Scholar 

  59. Buschke, N., Schröder, H., and Wittmann, C., Metabolic engineering of Corynebacterium glutamicum for production of 1,5-diaminopentane from hemicellulose, Biotechnol. J., 2011, vol. 6, no. 3, pp. 306–317. https://doi.org/10.1002/biot.201000304

    Article  CAS  PubMed  Google Scholar 

  60. Kawaguchi, H., Vertes, A.A., Okino, S., Inui, M., and Yukawa, H., Engineering of a xylose metabolic pathway in Corynebacterium glutamicum,Appl. Environ. Microbiol., 2006, vol. 72, no. 5, pp. 3418–3428. https://doi.org/10.1128/AEM.72.5.3418-3428.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ryu, S. and Karim, M.N., A whole cell biocatalyst for cellulosic ethanol production from dilute acid-pretreated corn stover hydrolyzates, Appl. Microbiol. Biotechnol., 2011, vol. 91, no. 3, pp. 529–542. https://doi.org/10.1007/s00253-011-3261-z

    Article  CAS  PubMed  Google Scholar 

  62. Mori, M. and Shiio, I., Pyruvate formation and sugar metabolism in an amino acid-producing bacterium Brevibacterium flavum,Agric. Biol. Chem., 1987, vol. 51, no. 1, pp. 129–138. https://doi.org/10.1271/bbb1961.51.129

    Article  CAS  Google Scholar 

  63. Parche, S., Burkovski, A., Sprenger, G.A., Weil, B., Kramer, R., and Titgemeyer, F., Corynebacterium glutamicum: a dissection of the PTS, J. Mol. Microbiol. Biotechnol., 2001, vol. 3, no. 3, pp. 423–428.

    CAS  PubMed  Google Scholar 

  64. Ikeda, M., Sugar transport systems in Corynebacterium glutamicum: features and applications to strain development, Appl. Microbiol. Biotechnol., 2012, vol. 96, no. 5, pp. 1191–1200. https://doi.org/10.1007/s00253-012-4488-z

    Article  CAS  PubMed  Google Scholar 

  65. Neuner, A. and Heinzle, E., Mixed glucose and lactate uptake by Corynebacterium glutamicum through metabolic engineering, Biotechnol. J., 2011, vol. 6, no. 3, pp. 318–329. https://doi.org/10.1002/biot.201000307

    Article  CAS  PubMed  Google Scholar 

  66. Ikeda, M., Mizuno, Y., Awane, S., Hayashi, M., Mitsuhashi, S., and Takeno, S., Identification and application of a different glucose uptake system that functions as an alternative to the phosphotransferase system in Corynebacterium glutamicum,Appl. Microbiol. Biotechnol., 2011, vol. 90, no. 4, pp. 1443–1451. https://doi.org/10.1007/s00253-011-3210-x

    Article  CAS  PubMed  Google Scholar 

  67. Lindner, S.N., Seibold, G.M., Henrich, A., Kramer, R., and Wendisch, V.F., Phosphotransferase system independent glucose utilization in Corynebacterium glutamicum by inositol permeases and glucokinases, Appl. Environ. Microbiol., 2011, vol. 77, no. 11, pp. 3571–3581. https://doi.org/10.1128/AEM.02713-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tan, J.M., Wong, E.S., Kirkpatrick, D.S., Pletnikova, O., Ko, H.S., Tay, S.P., Ho, M.W., Troncoso, J., Gygi, S.P., Lee, M.K., Dawson, V.L., Dawson, T.M., and Lim, K.L., Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases, Hum. Mol. Genet., 2008, vol. 17, no. 3, pp. 431–439. https://doi.org/10.1093/hmg/ddm320

    Article  CAS  PubMed  Google Scholar 

  69. Kawaguchi, A., Ikawa, T., and Kasukawa, T., Ueda, H.R., Kurimoto, K., Saitou, M., and Matsuzaki, F., Single cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis, Development, 2008, vol. 135, no. 18, pp. 3113–3124. https://doi.org/10.1242/dev.022616

    Article  CAS  PubMed  Google Scholar 

  70. Meiswinkel, T.M., Gopinath, V., Lindner, S.N., Nampoothiri, K.M., and Wendisch, V.F., Accelerated pentose utilization by Corynebacterium glutamicum for accelerated production of lysine, glutamate, ornithine and putrescine, Microb. Biotechnol., 2013, vol. 6, no. 2, pp. 131–140.

    Article  Google Scholar 

  71. Radek, A., Krumbach, K., Gaetgens, J., Wendisch, V.F., Wiechert, W., Bott, M., Noack, S., and Marienhagen, J., Engineering of Corynebacterium glutamicum for minimized carbon loss during utilization of D-xylose containing substrates, J. Biotechnol., 2014, vol. 192, pp. 156–160. https://doi.org/10.1016/j.jbiotec.2014.09.026

    Article  CAS  PubMed  Google Scholar 

  72. Marin, K. and Krämer, R., Amino acid transport systems in biotechnologically relevant bacteria, in Amino Acid Biosynthesis—Pathways, Regulation and Metabolic Engineering, Wendisch, V.F., Ed., Microbiology Monographs, Berlin: Springer, 2007, vol. 5, pp. 289–325. https://doi.org/10.1007/7171_2006_069

  73. Eggeling, L., Exporters for production of amino acids and other small molecules, Adv. Biochem. Eng. Biotechnol., 2017, vol. 159, pp. 199–225. https://doi.org/10.1007/10_2016_32

    Article  CAS  PubMed  Google Scholar 

  74. Blombach, B., Hans, S., and Bathe, B., and EikmannsB.J., Acetohydroxyacid synthase, a novel target for improvement of L-lysine production by Corynebacterium glutamicum,Appl. Environ. Microbiol., 2009, vol. 75, no. 2, pp. 419–427. https://doi.org/10.1128/AEM.01844-08

    Article  CAS  PubMed  Google Scholar 

  75. Unthan, S., Radek, A., Wiechert, W., Oldiges, M., and Noack, S., Bioprocess automation on a mini pilot plant enables fast quantitative microbial phenotyping, Microb. Cell Factories, 2015, vol. 14, p. 32. https://doi.org/10.1186/s12934-015-0216-6

  76. Pérez-García, F., Peters-Wendisch, P., and Wendisch, V.F., Engineering Corynebacterium glutamicum for fast production of L-lysine and L-pipecolic acid, Appl. Microbiol. Biotechnol., 2016, vol. 100, no. 18, pp. 8075–8090. https://doi.org/10.1007/s00253-016-7682-6

    Article  CAS  PubMed  Google Scholar 

  77. Henke, N.A., Wiebe, D., Perez-Garcia, F., Peters-Wendisch, P., and Wendisch, V.F., Coproduction of cell-bound and secreted value-added compounds: simultaneous production of carotenoids and amino acids by Corynebacterium glutamicum,Bioresour. Technol., 2018, vol. 247, pp. 744–752. https://doi.org/10.1016/j.biortech.2017.09.167

    Article  CAS  PubMed  Google Scholar 

  78. Kind, S., Neubauer, S., Becker, J., Yamamoto, M., Volkert, M., Abendroth, G.V., and Zelder, O., and WittmannC. From zero to hero-production of biobased nylon from renewable resources using engineered Corynebacterium glutamicum,Metab. Eng., 2014, vol. 25, pp. 113–123. https://doi.org/10.1016/j.ymben.2014.05.007

    Article  CAS  PubMed  Google Scholar 

  79. Rohles, C.M., Gießelmann, G., Kohlstedt, M., Wittman, Ch., and Becker, J., Systems metabolic engineering of Corynebacterium glutamicum for the production of the carbon-5 platform chemicals 5-aminovalerate and glutarate, Microb. Cell Fact., 2016, vol. 15, no. 1, pp. 154–167. https://doi.org/10.1186/s12934-016-0553-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Pérez-García, F., Risse, J.M., Friesh, K., and Wendisch, V.F., Fermentative production of L-pipecolic acid from glucose and alternative carbon sources, Biotech. J., 2017, vol. 12, no. 7. https://doi.org/10.1002/biot.201600646

  81. Goh, C.S. and Lee, K.T., Conceptual macroalgae-based third-generation bioethanol (TGB) biorefinery in Sabah. Malaysia as an underlay for renewable and sustainable development, Renew. Sustain. Energy Rev., 2010, vol. 14, pp. 842–848. https://doi.org/10.1016/j.rser.2009.10.001

    Article  CAS  Google Scholar 

  82. Wang, X., Liu, X., and Wang, G., Two-stage hydrolysis of invasive algal feedstock for ethanol fermentation, J. Integr. Plant Biol., 2011, vol. 53, no. 3, pp. 246–252. https://doi.org/10.1111/j.1744-7909.2010.01024.x

    Article  CAS  PubMed  Google Scholar 

  83. Peng, X., Okai, N., Vertes, A.A., Inatomi, K., Inui, M., and Yukawa, H., Characterization of the mannitol catabolic operon of Corynebacterium glutamicum,Appl. Microbiol. Biotechnol., 2011, vol. 91, no. 5, pp. 1375–1387. https://doi.org/10.1007/s00253-011-3352-x

    Article  CAS  PubMed  Google Scholar 

  84. Takeno, S., Murata, R., Kobayashi, R., Mitsuhashi, S., and Ikeda, M., Engineering of Corynebacterium glutamicum with an NADPH-generating glycolytic pathway for L-lysine production, Appl. Environ. Microbiol., 2010, vol. 76, no. 21, pp. 7154–7160. https://doi.org/10.1128/AEM.01464-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bommareddy, R.R., Chen, Z., Rappert, S., and Zeng, A.P., A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase, Metab. Eng., 2014, vol. 25, pp. 30–37. https://doi.org/10.1016/j.ymben.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  86. Eggeling, L. and Bott, M., A giant market and a powerful metabolism: L-lysine provided by Corynebacterium glutamicum,Appl. Microbiol. Biotechnol., 2015, vol. 99, no. 8, pp. 3387–3394.

    Article  CAS  Google Scholar 

  87. Marx, A., Hans, S., Mockel, B., Bathe, B., de Graaf, A.A., McCormack, A.C., Stapleton, C., Burke, K., O’Donohue, M., and Dunican, L.K., Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum,J. Biotechnol., 2003, vol. 104, pp. 185–197. https://doi.org/10.1016/S0168-1656(03)00153-6

    Article  CAS  PubMed  Google Scholar 

  88. Ohnishi, J., Katahira, R., Mitsuhashi, S., Kakita, S., and Ikeda, M., A novel gnd mutation leading to increased L-lysine production in Corynebacterium glutamicum,FEMS Microbiol. Lett., 2005, vol. 242, pp. 265–274. https://doi.org/10.1016/j.femsle.2004.11.014

    Article  CAS  PubMed  Google Scholar 

  89. Buchholz, J., Schwentner, A., Brunnenkan, B., Gabris, C., Grimm, S., Gerstmeir, R., Takors, R., Eikmanns Eikmanns, B.J., and Blombach, B., Platform engineering of Corynebacterium glutamicum with reduced pyruvate dehydrogenase complex activity for improved production of L-lysine, L-valine, and 2-ketoisovalerate, Appl. Environ. Microbiol., 2013, vol. 79, no. 18, pp. 5566–5575. https://doi.org/10.1128/AEM.01741-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Becker, J., Klopprogge, C., Herold, A., Zelder, O., Bolten, C.J., and Wittmann, C., Metabolic flux engineering of L-lysine production in Corynebacterium glutamicum-over expression and modification of G6P dehydrogenase, J. Biotechnol., 2007, vol. 132, no. 2, pp. 99–109. https://doi.org/10.1016/j.jbiotec.2007.05.026

    Article  CAS  PubMed  Google Scholar 

  91. Becker, J. and Wittmann, C., Advanced biotechnology: metabolically engineered cells for the bio-based production of chemicals and fuels, materials, and healthcare products, Angew. Chem., Int. Ed., 2015, vol. 54, pp. 3328–3350. https://doi.org/10.1002/anie.201409033

    Article  CAS  Google Scholar 

  92. Cleto, S., Jensen, J.V., Wendisch, V.F., and Lu, T.K., Corynebacterium glutamicum metabolic engineering with CRISPR interference (CRISPRi), ACS Synth. Biol., 2016, no. 5, pp. 375–385. https://doi.org/10.1021/acssynbio.5b00216

  93. Park, J., Shin, H., Lee, S.-M., Um, Y., and Woo, H.M., RNA-guided single/double gene repressions in Corynebacterium glutamicum using an efficient CRISPR interference and its application to industrial strain, Microb. Cell Fact., 2018, vol. 17, no. 4. https://doi.org/10.1186/s12934-017-0843-1

  94. Cho, J.S., Choi, K.R., Prabowo, C.P.S., Shin, J.H., Yang, D., Jang, J., and Lee, S.Y., CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum,Metabol. Eng., 2017, no. 42, pp. 157–167. https://doi.org/10.1016/j.ymben.2017.06.010

  95. Shuman, S. and Glickman, M.S., Bacterial DNA repair by non-homologous end joining, Nat. Rev. Microbiol., 2007, vol. 5, no. 11, pp. 852–861. https://doi.org/10.1038/nrmicro1768

    Article  CAS  PubMed  Google Scholar 

  96. Wang, B., Qitiao, HuQ., Zhang, Y., and Shi, R., Chai, X., Liu, Z., Shang, X., Zhang, Y., and Wen, T., A RecET-assisted CRISPR–Cas9 genome editing in Corynebacterium glutamicum,Microb. Cell Fact., 2018, vol. 17, no. 63, pp. 1–16. https://doi.org/10.1186/s12934-018-0910-2

    Article  CAS  Google Scholar 

Download references

Funding

This study did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.

Author information

Authors and Affiliations

  1. Institute for Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, 04123, Kyiv, Ukraine

    G. S. Andriiash, O. S. Sekan, O. O. Tigunova, Ya. B. Blume & S. M. Shulga

  2. Division of Wood Science and Engineering, Department of Engineering Sciences and Mathematics, Lulea University of Technology, 93187, Skelleftea, Sweden

    O. S. Sekan

Authors
  1. G. S. Andriiash
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. S. Sekan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. O. Tigunova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ya. B. Blume
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. M. Shulga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. M. Shulga.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Additional information

Translated by V. Mittova

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andriiash, G.S., Sekan, O.S., Tigunova, O.O. et al. Metabolic Engineering of Lysine Producing Corynebacterium glutamicum Strains. Cytol. Genet. 54, 137–146 (2020). https://doi.org/10.3103/S0095452720020024

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452720020024

Search

Navigation