Genome-Reduced Corynebacterium glutamicum Fit for Biotechnological Applications

  • Volker F. WendischEmail author


Genome minimization ultimately leads to the smallest genome sustaining life of a given cell; however, growth of this cell may be very slow and may require multiple supplements, e.g., to overcome amino acid auxotrophies. By contrast, genome reduction of industrially relevant bacteria such as Corynebacterium glutamicum does not aim at generating minimal cells. Rather chassis cells are developed that are as fit as the wild type with respect to a target function, for example, growth of C. glutamicum in glucose minimal medium. Thus, a balance between reducing the burden of expressed genes and maintaining fast growth with glucose without the requirement for supplements such as amino acids is required. Here, the application of this concept to C. glutamicum is discussed. Moreover, an outlook on how the advent of genome editing by CRISPR-Cas9 or CRISPR-Cas12a(Cpf1) impacts genome reduction and how highly parallel genome editing must be met by highly parallel strain characterization is presented. Finally, metabolic engineering approaches for the overproduction of amino acids, organic acids, terpenoids, and diamines making use of genome-reduced C. glutamicum strains are detailed.


Corynebacterium glutamicum Genome reduction Amino acid production Metabolic engineering Fine chemicals Two-step homologous recombination, CRISPR/Cas9 



VFW gratefully acknowledges support by ERACoBiotech grant INDIE (BMEL 22023517), by the Indo-German project BIOCON (BMBF 01DQ17009) and by funding from the state of North Rhine-Westphalia (NRW) and the “European Regional Development Fund (EFRE)”, Project “ClusterIndustrial Biotechnology (CLIB) Kompetenzzentrum Biotechnologie (CKB)” (34.EFRE-0300095/1703FI04).


  1. Auchter M, Cramer A, Huser A, Ruckert C, Emer D, Schwarz P, Arndt A, Lange C, Kalinowski J, Wendisch VF, Eikmanns BJ (2011) RamA and RamB are global transcriptional regulators in Corynebacterium glutamicum and control genes for enzymes of the central metabolism. J Biotechnol 154(2–3):126–139. CrossRefPubMedGoogle Scholar
  2. Baumgart M, Unthan S, Ruckert C, Sivalingam J, Grunberger A, Kalinowski J, Bott M, Noack S, Frunzke J (2013) Construction of a prophage-free variant of Corynebacterium glutamicum ATCC 13032 for use as a platform strain for basic research and industrial biotechnology. Appl Environ Microbiol 79(19):6006–6015. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baumgart M, Unthan S, Kloss R, Radek A, Polen T, Tenhaef N, Muller MF, Kuberl A, Siebert D, Bruhl N, Marin K, Hans S, Kramer R, Bott M, Kalinowski J, Wiechert W, Seibold G, Frunzke J, Ruckert C, Wendisch VF, Noack S (2018) Corynebacterium glutamicumchassis C1∗: building and testing a novel platform host for synthetic biology and industrial biotechnology. ACS Synth Biol 7(1):132–144. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Becker J, Wittmann C (2012) Bio-based production of chemicals, materials and fuels -Corynebacterium glutamicum as versatile cell factory. Curr Opin Biotechnol 23(4):631–640. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Binder D, Frohwitter J, Mahr R, Bier C, Grunberger A, Loeschcke A, Peters-Wendisch P, Kohlheyer D, Pietruszka J, Frunzke J, Jaeger KE, Wendisch VF, Drepper T (2016) Light-controlled cell factories: employing photocaged isopropyl-beta-D-thiogalactopyranoside for light-mediated optimization of lac promoter-based gene expression and (+)-Valencene biosynthesis in Corynebacterium glutamicum. Appl Environ Microbiol 82(20):6141–6149. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Blombach B, Riester T, Wieschalka S, Ziert C, Youn JW, Wendisch VF, Eikmanns BJ (2011) Corynebacterium glutamicum tailored for efficient isobutanol production. Appl Environ Microbiol 77(10):3300–3310. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cameron Coates R, Blaskowski S, Szyjka S, van Rossum HM, Vallandingham J, Patel K, Serber Z, Dean J (2019) Systematic investigation of CRISPR-Cas9 configurations for flexible and efficient genome editing in Corynebacterium glutamicum NRRL-B11474. J Ind Microbiol Biotechnol 46(2):187–201. CrossRefPubMedGoogle Scholar
  8. Chassagnole C, Letisse F, Diano A, Lindley ND (2002) Carbon flux analysis in a pantothenate overproducing Corynebacterium glutamicum strain. Mol Biol Rep 29(1–2):129–134CrossRefGoogle Scholar
  9. Chen Z, Huang J, Wu Y, Wu W, Zhang Y, Liu D (2017) Metabolic engineering of Corynebacterium glutamicum for the production of 3-hydroxypropionic acid from glucose and xylose. Metab Eng 39:151–158. CrossRefPubMedGoogle Scholar
  10. Cheng F, Luozhong S, Yu H, Guo Z (2019) Biosynthesis of chondroitin in engineered Corynebacterium glutamicum. J Microbiol Biotechnol 29:392. CrossRefPubMedGoogle Scholar
  11. Cho JS, Choi KR, Prabowo CPS, Shin JH, Yang D, Jang J, Lee SY (2017) CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum. Metab Eng 42:157–167. CrossRefPubMedGoogle Scholar
  12. Choi JW, Yim SS, Kim MJ, Jeong KJ (2015) Enhanced production of recombinant proteins with Corynebacterium glutamicum by deletion of insertion sequences (IS elements). Microb Cell Factories 14:207. CrossRefGoogle Scholar
  13. Cleto S, Jensen JV, Wendisch VF, Lu TK (2016) Corynebacterium glutamicummetabolic engineering with CRISPR interference (CRISPRi). ACS Synth Biol 5(5):375–385. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Contador CA, Rizk ML, Asenjo JA, Liao JC (2009) Ensemble modeling for strain development of L-lysine-producingEscherichia coli. Metab Eng 11(4–5):221–233. CrossRefPubMedGoogle Scholar
  15. Eberhardt D, Jensen JV, Wendisch VF (2014) L-citrulline production by metabolically engineered Corynebacterium glutamicum from glucose and alternative carbon sources. AMB Express 4:85CrossRefGoogle Scholar
  16. Eggeling L, Bott M, Marienhagen J (2015) Novel screening methods--biosensors. Curr Opin Biotechnol 35:30–36. CrossRefPubMedGoogle Scholar
  17. Engels V, Wendisch VF (2007) The DeoR-type regulator SugR represses expression of ptsG in Corynebacterium glutamicum. J Bacteriol 189(8):2955–2966CrossRefGoogle Scholar
  18. Engels V, Lindner SN, Wendisch VF (2008) The global repressor SugR controls expression of genes of glycolysis and of the L-lactate dehydrogenase LdhA in Corynebacterium glutamicum. J Bacteriol 190(24):8033–8044. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007) A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol Syst Biol 3:121. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Fischer F, Poetsch A (2006) Protein cleavage strategies for an improved analysis of the membrane proteome. Proteome Sci 4:2CrossRefGoogle Scholar
  21. Frazzetto G (2003) White biotechnology. EMBO Rep 4(9):835–837. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Freiherr von Boeselager R, Pfeifer E, Frunzke J (2018) Cytometry meets next-generation sequencing - RNA-Seq of sorted subpopulations reveals regional replication and iron-triggered prophage induction in Corynebacterium glutamicum. Sci Rep 8(1):14856. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Freudl R (2017) Beyond amino acids: use of the Corynebacterium glutamicum cell factory for the secretion of heterologous proteins. J Biotechnol 258:101–109. CrossRefPubMedGoogle Scholar
  24. Freudl R (2018) Signal peptides for recombinant protein secretion in bacterial expression systems. Microb Cell Factories 17:52. CrossRefGoogle Scholar
  25. Frunzke J, Bramkamp M, Schweitzer JE, Bott M (2008) Population heterogeneity in Corynebacterium glutamicum ATCC 13032 caused by prophage CGP3. J Bacteriol 190(14):5111–5119CrossRefGoogle Scholar
  26. Gorshkova NV, Lobanova JS, Tokmakova IL, Smirnov SV, Akhverdyan VZ, Krylov AA, Mashko SV (2018) Mu-driven transposition of recombinant mini-Mu unit DNA in the Corynebacterium glutamicum chromosome. Appl Microbiol Biotechnol 102(6):2867–2884. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hansmeier N, Chao TC, Puhler A, Tauch A, Kalinowski J (2006) The cytosolic, cell surface and extracellular proteomes of the biotechnologically important soil bacterium Corynebacterium efficiens YS-314 in comparison to those of Corynebacterium glutamicum ATCC 13032. Proteomics 6(1):233–250CrossRefGoogle Scholar
  28. Heider SA, Peters-Wendisch P, Netzer R, Stafnes M, Brautaset T, Wendisch VF (2014a) Production and glucosylation of C50 and C 40 carotenoids by metabolically engineered Corynebacterium glutamicum. Appl Microbiol Biotechnol 98(3):1223–1235. CrossRefPubMedGoogle Scholar
  29. Heider SA, Wolf N, Hofemeier A, Peters-Wendisch P, Wendisch VF (2014b) Optimization of the IPP precursor supply for the production of lycopene, decaprenoxanthin and astaxanthin by Corynebacterium glutamicum. Front Bioeng Biotechnol 2:28. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Helfrich S, Pfeifer E, Kramer C, Sachs CC, Wiechert W, Kohlheyer D, Noh K, Frunzke J (2015) Live cell imaging of SOS and prophage dynamics in isogenic bacterial populations. Mol Microbiol 98(4):636–650. CrossRefPubMedGoogle Scholar
  31. Hemmerich J, Rohe P, Kleine B, Jurischka S, Wiechert W, Freudl R, Oldiges M (2016) Use of a Sec signal peptide library from Bacillus subtilis for the optimization of cutinase secretion in Corynebacterium glutamicum. Microb Cell Factories 15(1):208. CrossRefGoogle Scholar
  32. Hemmerich J, Wiechert W, Oldiges M (2017) Automated growth rate determination in high-throughput microbioreactor systems. BMC Res Notes 10(1):617. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hemmerich J, Tenhaef N, Steffens C, Kappelmann J, Weiske M, Reich SJ, Wiechert W, Oldiges M, Noack S (2018a) Less sacrifice, more insight: repeated low-volume sampling of microbioreactor cultivations enables accelerated deep phenotyping of microbial strain libraries. Biotechnol J. CrossRefGoogle Scholar
  34. Hemmerich J, Noack S, Wiechert W, Oldiges M (2018b) Microbioreactor systems for accelerated bioprocess development. Biotechnol J 13(4):e1700141. CrossRefPubMedGoogle Scholar
  35. Hemmerich J, Moch M, Jurischka S, Wiechert W, Freudl R, Oldiges M (2019) Combinatorial impact of sec signal peptides from Bacillus subtilis and bioprocess conditions on heterologous cutinase secretion by Corynebacterium glutamicum. Biotechnol Bioeng 116(3):644–655. CrossRefPubMedGoogle Scholar
  36. Henke NA, Heider SA, Peters-Wendisch P, Wendisch VF (2016) Production of the marine carotenoid astaxanthin by metabolically engineered Corynebacterium glutamicum. Mar Drugs 14(7):124. CrossRefPubMedCentralGoogle Scholar
  37. Henke NA, Heider SAE, Hannibal S, Wendisch VF, Peters-Wendisch P (2017) Isoprenoid pyrophosphate-dependent transcriptional regulation of Carotenogenesis in Corynebacterium glutamicum. Front Microbiol 8:633. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Henke NA, Wiebe D, Perez-Garcia F, Peters-Wendisch P, Wendisch VF (2018a) Coproduction of cell-bound and secreted value-added compounds: simultaneous production of carotenoids and amino acids by Corynebacterium glutamicum. Bioresour Technol 247:744–752. CrossRefPubMedGoogle Scholar
  39. Henke NA, Wichmann J, Baier T, Frohwitter J, Lauersen KJ, Risse JM, Peters-Wendisch P, Kruse O, Wendisch VF (2018b) Patchoulol production with metabolically engineered Corynebacterium glutamicum. Genes (Basel) 9(4):219. CrossRefGoogle Scholar
  40. Hermann T, Finkemeier M, Pfefferle W, Wersch G, Kramer R, Burkovski A (2000) Two-dimensional electrophoretic analysis of Corynebacterium glutamicum membrane fraction and surface proteins. Electrophoresis 21(3):654–659CrossRefGoogle Scholar
  41. Hoffmann J, Altenbuchner J (2014) Hyaluronic acid production with Corynebacterium glutamicum: effect of media composition on yield and molecular weight. J Appl Microbiol 117(3):663–678. CrossRefPubMedGoogle Scholar
  42. Huang J, Wu Y, Wu W, Zhang Y, Liu D, Chen Z (2017) Cofactor recycling for co-production of 1,3-propanediol and glutamate by metabolically engineered Corynebacterium glutamicum. Sci Rep 7:42246. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Huber I, Palmer DJ, Ludwig KN, Brown IR, Warren MJ, Frunzke J (2017) Construction of recombinant Pdu metabolosome shells for small molecule production in Corynebacterium glutamicum. ACS Synth Biol 6(11):2145–2156. CrossRefPubMedGoogle Scholar
  44. Ikeda M (2003) Amino acid production processes. Adv Biochem Eng Biotechnol 79:1–35PubMedGoogle Scholar
  45. Ikeda M, Nakagawa S (2003) The Corynebacterium glutamicum genome: features and impacts on biotechnological processes. Appl Microbiol Biotechnol 62(2–3):99–109CrossRefGoogle Scholar
  46. Imao K, Konishi R, Kishida M, Hirata Y, Segawa S, Adachi N, Matsuura R, Tsuge Y, Matsumoto T, Tanaka T, Kondo A (2017) 1,5-Diaminopentane production from xylooligosaccharides using metabolically engineered Corynebacterium glutamicum displaying beta-xylosidase on the cell surface. Bioresour Technol 245(Pt B):1684–1691. CrossRefPubMedGoogle Scholar
  47. Jäger W, Schäfer A, Pühler A, Labes G, Wohlleben W (1992) Expression of the Bacillus subtilis sacB gene leads to sucrose sensitivity in the gram-positive bacterium Corynebacterium glutamicum but not in Streptomyces lividans. J Bacteriol 174(16):5462–5465CrossRefGoogle Scholar
  48. Jensen JV, Eberhardt D, Wendisch VF (2015) Modular pathway engineering of Corynebacterium glutamicum for production of the glutamate-derived compounds ornithine, proline, putrescine, citrulline, and arginine. J Biotechnol 214:85–94. CrossRefPubMedGoogle Scholar
  49. Jiang Y, Qian F, Yang J, Liu Y, Dong F, Xu C, Sun B, Chen B, Xu X, Li Y, Wang R, Yang S (2017) CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum. Nat Commun 8:15179. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Jo SJ, Matsumoto K, Leong CR, Ooi T, Taguchi S (2007) Improvement of poly(3-hydroxybutyrate) [P(3HB)] production in Corynebacterium glutamicum by codon optimization, point mutation and gene dosage of P(3HB) biosynthetic genes. J Biosci Bioeng 104(6):457–463CrossRefGoogle Scholar
  51. Jorge JM, Leggewie C, Wendisch VF (2016) A new metabolic route for the production of gamma-aminobutyric acid by Corynebacterium glutamicum from glucose. Amino Acids 48:2519. CrossRefPubMedGoogle Scholar
  52. Jorge JM, Nguyen AQ, Perez-Garcia F, Kind S, Wendisch VF (2017a) Improved fermentative production of gamma-aminobutyric acid via the putrescine route: systems metabolic engineering for production from glucose, amino sugars, and xylose. Biotechnol Bioeng 114(4):862–873. CrossRefPubMedGoogle Scholar
  53. Jorge JMP, Perez-Garcia F, Wendisch VF (2017b) A new metabolic route for the fermentative production of 5-aminovalerate from glucose and alternative carbon sources. Bioresour Technol 245(Pt B):1701–1709. CrossRefPubMedGoogle Scholar
  54. Kalinowski J, Bathe B, Bartels D, Bischoff N, Bott M, Burkovski A, Dusch N, Eggeling L, Eikmanns BJ, Gaigalat L, Goesmann A, Hartmann M, Huthmacher K, Kramer R, Linke B, McHardy AC, Meyer F, Mockel B, Pfefferle W, Puhler A, Rey DA, Ruckert C, Rupp O, Sahm H, Wendisch VF, Wiegrabe I, Tauch A (2003) The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of L-aspartate-derived amino acids and vitamins. J Biotechnol 104(1–3):5–25CrossRefGoogle Scholar
  55. Kallscheuer N, Marienhagen J (2018) Corynebacterium glutamicum as platform for the production of hydroxybenzoic acids. Microb Cell Factories 17(1):70. CrossRefGoogle Scholar
  56. Kallscheuer N, Vogt M, Stenzel A, Gatgens J, Bott M, Marienhagen J (2016a) Construction of a Corynebacterium glutamicum platform strain for the production of stilbenes and (2S)-flavanones. Metab Eng 38:47–55. CrossRefPubMedGoogle Scholar
  57. Kallscheuer N, Vogt M, Kappelmann J, Krumbach K, Noack S, Bott M, Marienhagen J (2016b) Identification of the phd gene cluster responsible for phenylpropanoid utilization in Corynebacterium glutamicum. Appl Microbiol Biotechnol 100(4):1871–1881. CrossRefPubMedGoogle Scholar
  58. Kim EM, Um Y, Bott M, Woo HM (2015) Engineering of Corynebacterium glutamicum for growth and succinate production from levoglucosan, a pyrolytic sugar substrate. FEMS Microbiol Lett 362(19):fnv161. CrossRefPubMedGoogle Scholar
  59. Kind S, Becker J, Wittmann C (2013) Increased lysine production by flux coupling of the tricarboxylic acid cycle and the lysine biosynthetic pathway--metabolic engineering of the availability of succinyl-CoA in Corynebacterium glutamicum. Metab Eng 15:184–195. CrossRefPubMedGoogle Scholar
  60. Kirchner O, Tauch A (2003) Tools for genetic engineering in the amino acid-producing bacterium Corynebacterium glutamicum. J Biotechnol 104(1–3):287–299CrossRefGoogle Scholar
  61. Kitade Y, Hashimoto R, Suda M, Hiraga K, Inui M (2018) Production of 4-Hydroxybenzoic acid by an aerobic growth-arrested bioprocess using metabolically engineered Corynebacterium glutamicum. Appl Environ Microbiol 84(6):e02587–e02517. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kjeldsen KR, Nielsen J (2009) In silico genome-scale reconstruction and validation of the Corynebacterium glutamicum metabolic network. Biotechnol Bioeng 102(2):583–597. CrossRefPubMedGoogle Scholar
  63. Klatt S, Brammananth R, O’Callaghan S, Kouremenos KA, Tull D, Crellin PK, Coppel RL, McConville MJ (2018) Identification of novel lipid modifications and intermembrane dynamics in Corynebacterium glutamicum using high-resolution mass spectrometry. J Lipid Res 59(7):1190–1204. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 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(2):253–265. CrossRefPubMedGoogle Scholar
  65. Krings E, Krumbach K, Bathe B, Kelle R, Wendisch VF, Sahm H, Eggeling L (2006) Characterization of myo-inositol utilization by Corynebacterium glutamicum: the stimulon, identification of transporters, and influence on L-lysine formation. J Bacteriol 188(23):8054–8061CrossRefGoogle Scholar
  66. Kuberl A, Franzel B, Eggeling L, Polen T, Wolters DA, Bott M (2014) Pupylated proteins in Corynebacterium glutamicum revealed by MudPIT analysis. Proteomics 14(12):1531–1542. CrossRefPubMedGoogle Scholar
  67. Kuberl A, Polen T, Bott M (2016) The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin. Proc Natl Acad Sci U S A 113(17):4806–4811. CrossRefPubMedPubMedCentralGoogle Scholar
  68. Lee JH, Wendisch VF (2017) Production of amino acids –genetic and metabolic engineering approaches. Bioresour Technol 245(Pt B):1575–1587. CrossRefPubMedGoogle Scholar
  69. Lee JY, Seo J, Kim ES, Lee HS, Kim P (2013) Adaptive evolution of Corynebacterium glutamicum resistant to oxidative stress and its global gene expression profiling. Biotechnol Lett 35(5):709–717. CrossRefPubMedGoogle Scholar
  70. Leuchtenberger W, Huthmacher K, Drauz K (2005) Biotechnological production of amino acids and derivatives: current status and prospects. Appl Microbiol Biotechnol 69(1):1–8CrossRefGoogle Scholar
  71. Litsanov B, Brocker M, Bott M (2012) Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate. Appl Environ Microbiol 78(9):3325–3337. CrossRefPubMedPubMedCentralGoogle Scholar
  72. Litsanov B, Brocker M, Bott M (2013) Glycerol as a substrate for aerobic succinate production in minimal medium with Corynebacterium glutamicum. Microb Biotechnol 6(2):189–195. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 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(1):205. CrossRefGoogle Scholar
  74. Lubitz D, Wendisch VF (2016) Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiol 16(1):235. CrossRefPubMedPubMedCentralGoogle Scholar
  75. Lubitz D, Jorge JM, Perez-Garcia F, Taniguchi H, Wendisch VF (2016) Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum. Appl Microbiol Biotechnol 100(19):8465–8474. CrossRefPubMedGoogle Scholar
  76. Ma Q, Zhang Q, Xu Q, Zhang C, Li Y, Fan X, Xie X, Chen N (2017) Systems metabolic engineering strategies for the production of amino acids. Synth Syst Biotechnol 2(2):87–96. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Mahr R, Gätgens C, Gätgens J, Polen T, Kalinowski J, Frunzke J (2015) Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metab Eng 32:184–194. CrossRefPubMedGoogle Scholar
  78. Matsuda Y, Itaya H, Kitahara Y, Theresia NM, Kutukova EA, Yomantas YA, Date M, Kikuchi Y, Wachi M (2014) Double mutation of cell wall proteins CspB and PBP1a increases secretion of the antibody fab fragment from Corynebacterium glutamicum. Microb Cell Factories 13(1):56. CrossRefGoogle Scholar
  79. Milke L, Kallscheuer N, Kappelmann J, Marienhagen J (2019) Tailoring Corynebacterium glutamicum towards increased malonyl-CoA availability for efficient synthesis of the plant pentaketide noreugenin. Microb Cell Factories 18(1):71. CrossRefGoogle Scholar
  80. Mindt M, Risse JM, Gruss H, Sewald N, Eikmanns BJ, Wendisch VF (2018a) One-step process for production of N-methylated amino acids from sugars and methylamine using recombinant Corynebacterium glutamicum as biocatalyst. Sci Rep 8(1):12895. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Mindt M, Walter T, Risse JM, Wendisch VF (2018b) Fermentative production of N-Methylglutamate from glycerol by recombinant Pseudomonas putida. Front Bioeng Biotechnol 6:159. CrossRefPubMedPubMedCentralGoogle Scholar
  82. Mindt M, Heuser M, Wendisch VF (2019a) Xylose as preferred substrate for sarcosine production by recombinant Corynebacterium glutamicum. Bioresour Technol 281:135–142. CrossRefPubMedGoogle Scholar
  83. Mindt M, Hannibal S, Heuser M, Risse JM, Keerthi S, Madhavan Nampoothiri K, Wendisch VF (2019b) Fermentative production of N-alkylated glycine derivatives by recombinant Corynebacterium glutamicum using a mutant of imine reductase DpkA from Pseudomonas putida. Front Bioeng Biotechnol 7Google Scholar
  84. 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. CrossRefPubMedGoogle Scholar
  85. Mustafi N, Grünberger A, Mahr R, Helfrich S, Noh K, Blombach B, Kohlheyer D, Frunzke J (2014) Application of a genetically encoded biosensor for live cell imaging of L-valine production in pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum strains. PLoS One 9(1):e85731. CrossRefPubMedPubMedCentralGoogle Scholar
  86. Nanda AM, Heyer A, Kramer C, Grunberger A, Kohlheyer D, Frunzke J (2014) Analysis of SOS-induced spontaneous prophage induction in Corynebacterium glutamicum at the single-cell level. J Bacteriol 196(1):180–188. CrossRefPubMedPubMedCentralGoogle Scholar
  87. Neshat A, Mentz A, Ruckert C, Kalinowski J (2014) Transcriptome sequencing revealed the transcriptional organization at ribosome-mediated attenuation sites in Corynebacterium glutamicum and identified a novel attenuator involved in aromatic amino acid biosynthesis. J Biotechnol 190:55–63. CrossRefPubMedGoogle Scholar
  88. Ohnishi J, Mizoguchi H, Takeno S, Ikeda M (2008) Characterization of mutations induced by N-methyl-N’-nitro-N-nitrosoguanidine in an industrial Corynebacterium glutamicum strain. Mutat Res 649(1–2):239–244CrossRefGoogle Scholar
  89. Otten A, Brocker M, Bott M (2015) Metabolic engineering of Corynebacterium glutamicum for the production of itaconate. Metab Eng 30:156–165. CrossRefPubMedGoogle Scholar
  90. Park J, Shin H, Lee SM, Um Y, Woo HM (2018) RNA-guided single/double gene repressions in Corynebacterium glutamicum using an efficient CRISPR interference and its application to industrial strain. Microb Cell Factories 17(1):4. CrossRefGoogle Scholar
  91. Pauling J, Rottger R, Tauch A, Azevedo V, Baumbach J (2012) CoryneRegNet 6.0--updated database content, new analysis methods and novel features focusing on community demands. Nucleic Acids Res 40(Database issue):D610–D614. CrossRefPubMedGoogle Scholar
  92. Perez-Garcia F, Peters-Wendisch P, Wendisch VF (2016) Engineering Corynebacterium glutamicum for fast production of L-lysine and L-pipecolic acid. Appl Microbiol Biotechnol 100(18):8075–8090. CrossRefPubMedGoogle Scholar
  93. Perez-Garcia F, Max Risse J, Friehs K, Wendisch VF (2017) Fermentative production of L-pipecolic acid from glucose and alternative carbon sources. Biotechnol J 12(7). CrossRefGoogle Scholar
  94. Perez-Garcia F, Jorge JMP, Dreyszas A, Risse JM, Wendisch VF (2018) Efficient production of the dicarboxylic acid Glutarate by Corynebacterium glutamicum via a novel synthetic pathway. Front Microbiol 9:2589. CrossRefPubMedPubMedCentralGoogle Scholar
  95. Perez-Garcia F, Brito LF, Wendisch VF (2019) Function of L-pipecolic acid as compatible solute in Corynebacterium glutamicum as basis for its production under hyperosmolar conditions. Front Microbiol 10:340. CrossRefPubMedPubMedCentralGoogle Scholar
  96. Pfeifer E, Hunnefeld M, Popa O, Polen T, Kohlheyer D, Baumgart M, Frunzke J (2016) Silencing of cryptic prophages in Corynebacterium glutamicum. Nucleic Acids Res 44(21):10117–10131. CrossRefPubMedPubMedCentralGoogle Scholar
  97. Pfeifer E, Gatgens C, Polen T, Frunzke J (2017) Adaptive laboratory evolution of Corynebacterium glutamicum towards higher growth rates on glucose minimal medium. Sci Rep 7(1):16780. CrossRefPubMedPubMedCentralGoogle Scholar
  98. Pfeifer-Sancar K, Mentz A, Ruckert C, Kalinowski J (2013) Comprehensive analysis of the Corynebacterium glutamicum transcriptome using an improved RNAseq technique. BMC Genomics 14(1):888. CrossRefPubMedPubMedCentralGoogle Scholar
  99. Rohles CM, Giesselmann G, Kohlstedt M, Wittmann C, Becker J (2016) Systems metabolic engineering of Corynebacterium glutamicum for the production of the carbon-5 platform chemicals 5-aminovalerate and glutarate. Microb Cell Factories 15(1):154. CrossRefGoogle Scholar
  100. Ruwe M, Kalinowski J, Persicke M (2017) Identification and functional characterization of small alarmone synthetases in Corynebacterium glutamicum. Front Microbiol 8:1601. CrossRefPubMedPubMedCentralGoogle Scholar
  101. Ruwe M, Ruckert C, Kalinowski J, Persicke M (2018) Functional characterization of a small alarmone hydrolase in Corynebacterium glutamicum. Front Microbiol 9:916. CrossRefPubMedPubMedCentralGoogle Scholar
  102. Schaffer S, Weil B, Nguyen VD, Dongmann G, Gunther K, Nickolaus M, Hermann T, Bott M (2001) A high-resolution reference map for cytoplasmic and membrane-associated proteins of Corynebacterium glutamicum. Electrophoresis 22(20):4404–4422CrossRefGoogle Scholar
  103. Schluesener D, Rogner M, Poetsch A (2007) Evaluation of two proteomics technologies used to screen the membrane proteomes of wild-type Corynebacterium glutamicum and an L-lysine-producing strain. Anal Bioanal Chem 389(4):1055–1064CrossRefGoogle Scholar
  104. Schneider J, Wendisch VF (2011) Biotechnological production of polyamines by bacteria: recent achievements and future perspectives. Appl Microbiol Biotechnol 91(1):17–30. CrossRefPubMedGoogle Scholar
  105. Schulte J, Baumgart M, Bott M (2017) Identification of the cAMP phosphodiesterase CpdA as novel key player in cAMP-dependent regulation in Corynebacterium glutamicum. Mol Microbiol 103(3):534–552. CrossRefPubMedGoogle Scholar
  106. Sgobba E, Stumpf AK, Vortmann M, Jagmann N, Krehenbrink M, Dirks-Hofmeister ME, Moerschbacher B, Philipp B, Wendisch VF (2018) Synthetic Escherichia coli-Corynebacterium glutamicum consortia for L-lysine production from starch and sucrose. Bioresour Technol 260:302–310. CrossRefPubMedGoogle Scholar
  107. Shinfuku Y, Sorpitiporn N, Sono M, Furusawa C, Hirasawa T, Shimizu H (2009) Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum. Microb Cell Factories 8:43. CrossRefGoogle Scholar
  108. Siebert D, Wendisch VF (2015) Metabolic pathway engineering for production of 1,2-propanediol and 1-propanol by Corynebacterium glutamicum. Biotechnol Biofuels 8:91. CrossRefPubMedPubMedCentralGoogle Scholar
  109. Siedler S, Schendzielorz G, Binder S, Eggeling L, Bringer S, Bott M (2014) SoxR as a single-cell biosensor for NADPH-consuming enzymes in Escherichia coli. ACS Synth Biol 3(1):41–47. CrossRefPubMedGoogle Scholar
  110. Sindelar G, Wendisch VF (2007) Improving lysine production by Corynebacterium glutamicum through DNA microarray-based identification of novel target genes. Appl Microbiol Biotechnol 76(3):677–689. CrossRefPubMedGoogle Scholar
  111. Smirnov SV, Kodera T, Samsonova NN, Kotlyarova VA, Rushkevich NY, Kivero AD, Sokolov PM, Hibi M, Ogawa J, Shimizu S (2010) Metabolic engineering of Escherichia coli to produce (2S, 3R, 4S)-4-hydroxyisoleucine. Appl Microbiol Biotechnol 88(3):719–726. CrossRefPubMedGoogle Scholar
  112. Smith KM, Cho KM, Liao JC (2010) Engineering Corynebacterium glutamicum for isobutanol production. Appl Microbiol Biotechnol 87(3):1045–1055. CrossRefPubMedPubMedCentralGoogle Scholar
  113. Steffen V, Otten J, Engelmann S, Radek A, Limberg M, Koenig BW, Noack S, Wiechert W, Pohl M (2016) A toolbox of genetically encoded FRET-based biosensors for rapid L-lysine analysis. Sensors (Basel) 16(10):1604. CrossRefGoogle Scholar
  114. Syukur Purwanto H, Kang MS, Ferrer L, Han SS, Lee JY, Kim HS, Lee JH (2018) Rational engineering of the shikimate and related pathways in Corynebacterium glutamicum for 4-hydroxybenzoate production. J Biotechnol 282:92–100. CrossRefPubMedGoogle Scholar
  115. Taniguchi H, Wendisch VF (2015) Exploring the role of sigma factor gene expression on production by Corynebacterium glutamicum: sigma factor H and FMN as example. Front Microbiol 6:740. CrossRefPubMedPubMedCentralGoogle Scholar
  116. Taniguchi H, Henke NA, Heider SAE, Wendisch VF (2017) Overexpression of the primary sigma factor gene sigA improved carotenoid production by Corynebacterium glutamicum: application to production of β-carotene and the non-native linear C50 carotenoid bisanhydrobacterioruberin. Metab Eng Comm 4:1–11. CrossRefGoogle Scholar
  117. Theodosiou E, Breisch M, Julsing MK, Falcioni F, Bühler B, Schmid A (2017) An artificial TCA cycle selects for efficient alpha-ketoglutarate dependent hydroxylase catalysis in engineered Escherichia coli. Biotechnol Bioeng 114(7):1511–1520. CrossRefPubMedGoogle Scholar
  118. Tsuge Y, Tateno T, Sasaki K, Hasunuma T, Tanaka T, Kondo A (2013) Direct production of organic acids from starch by cell surface-engineered Corynebacterium glutamicum in anaerobic conditions. AMB Express 3(1):72. CrossRefPubMedPubMedCentralGoogle Scholar
  119. Unthan S, Baumgart M, Radek A, Herbst M, Siebert D, Brühl N, Bartsch A, Bott M, Wiechert W, Marin K, Hans S, Krämer R, Seibold G, Frunzke J, Kalinowski J, Rückert C, Wendisch VF, Noack S (2015a) Chassis organism from Corynebacterium glutamicum—a top-down approach to identify and delete irrelevant gene clusters. Biotechnol J 10(2):290–301. CrossRefPubMedPubMedCentralGoogle Scholar
  120. Unthan S, Radek A, Wiechert W, Oldiges M, Noack S (2015b) Bioprocess automation on a mini pilot plant enables fast quantitative microbial phenotyping. Microb Cell Factories 14:32. CrossRefGoogle Scholar
  121. Veldmann KH, Minges H, Sewald N, Lee JH, Wendisch VF (2019a) Metabolic engineering of Corynebacterium glutamicum for the fermentative production of halogenated tryptophan. J Biotechnol 291:7–16. CrossRefPubMedGoogle Scholar
  122. Veldmann KH, Dachwitz S, Risse JM, Lee J-H, Sewald N, Wendisch VF (2019b) Bromination of L-tryptophan in a fermentative process with Corynebacterium glutamicum. Front Bioeng Biotechnol 7Google Scholar
  123. Walter F, Grenz S, Ortseifen V, Persicke M, Kalinowski J (2016) Corynebacterium glutamicum ggtB encodes a functional gamma-glutamyl transpeptidase with gamma-glutamyl dipeptide synthetic and hydrolytic activity. J Biotechnol 232:99–109. CrossRefPubMedGoogle Scholar
  124. Wang Y, Liu Y, Liu J, Guo Y, Fan L, Ni X, Zheng X, Wang M, Zheng P, Sun J, Ma Y (2018a) MACBETH: multiplex automated Corynebacterium glutamicum base editing method. Metab Eng 47:200–210. CrossRefPubMedGoogle Scholar
  125. Wang B, Hu Q, Zhang Y, Shi R, Chai X, Liu Z, Shang X, Wen T (2018b) A RecET-assisted CRISPR-Cas9 genome editing in Corynebacterium glutamicum. Microb Cell Factories 17(1):63. CrossRefGoogle Scholar
  126. Wendisch VF (2003) Genome-wide expression analysis in Corynebacterium glutamicum using DNA microarrays. J Biotechnol 104(1–3):273–285CrossRefGoogle Scholar
  127. Wendisch VF (2014) Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development. Curr Opin Biotechnol 30C:51–58. CrossRefGoogle Scholar
  128. Wendisch VF (2019) Metabolic engineering advances and prospects for amino acid production. Metab Eng.
  129. Wendisch VF, Bott M, Kalinowski J, Oldiges M, Wiechert W (2006) Emerging Corynebacterium glutamicum systems biology. J Biotechnol 124(1):74–92. CrossRefPubMedGoogle Scholar
  130. Wendisch VF, Brito LF, Gil Lopez M, Hennig G, Pfeifenschneider J, Sgobba E, Veldmann KH (2016) The flexible feedstock concept in industrial biotechnology: metabolic engineering of Escherichia coli, Corynebacterium glutamicum, Pseudomonas, Bacillus and yeast strains for access to alternative carbon sources. J Biotechnol 234:139–157. CrossRefPubMedGoogle Scholar
  131. Wiedenheft B, Sternberg SH, Doudna JA (2012) RNA-guided genetic silencing systems in bacteria and archaea. Nature 482(7385):331–338. CrossRefPubMedGoogle Scholar
  132. Wieschalka S, Blombach B, Bott M, Eikmanns BJ (2013) Bio-based production of organic acids with Corynebacterium glutamicum. Microb Biotechnol 6(2):87–102. CrossRefPubMedGoogle Scholar
  133. Wu W, Zhang Y, Liu D, Chen Z (2019) Efficient mining of natural NADH-utilizing dehydrogenases enables systematic cofactor engineering of lysine synthesis pathway of Corynebacterium glutamicum. Metab Eng 52:77–86. CrossRefPubMedGoogle Scholar
  134. Yomantas YAV, Abalakina EG, Lobanova JS, Mamontov VA, Stoynova NV, Mashko SV (2018) Complete nucleotide sequences and annotations of phi673 and phi674, two newly characterised lytic phages of Corynebacterium glutamicum ATCC 13032. Arch Virol 163(9):2565–2568. CrossRefPubMedPubMedCentralGoogle Scholar
  135. Zahoor A, Lindner SN, Wendisch VF (2012) Metabolic engineering of Corynebacterium glutamicum aimed at alternative carbon sources and new products. Comput Struct Biotechnol J 3:e201210004. CrossRefPubMedPubMedCentralGoogle Scholar
  136. Zha J, Zang Y, Mattozzi M, Plassmeier J, Gupta M, Wu X, Clarkson S, Koffas MAG (2018) Metabolic engineering of Corynebacterium glutamicum for anthocyanin production. Microb Cell Factories 17(1):143. CrossRefGoogle Scholar
  137. Zhang Q, Zheng X, Wang Y, Yu J, Zhang Z, Dele-Osibanjo T, Zheng P, Sun J, Jia S, Ma Y (2018) Comprehensive optimization of the metabolomic methodology for metabolite profiling of Corynebacterium glutamicum. Appl Microbiol Biotechnol 102(16):7113–7121. CrossRefPubMedGoogle Scholar
  138. Zhang Y, Shang X, Wang B, Hu Q, Liu S, Wen T (2019) Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome-scale metabolic network model for trans-4-hydroxyproline production. Biotechnol Bioeng 116(1):99–109. CrossRefPubMedGoogle Scholar
  139. Zhao FL, Zhang C, Tang Y, Ye BC (2016) A genetically encoded biosensor for in vitro and in vivo detection of NADP. Biosens Bioelectron 77:901–906. CrossRefPubMedGoogle Scholar
  140. Zhou LB, Zeng AP (2015a) Exploring lysine riboswitch for metabolic flux control and improvement of L-lysine synthesis in Corynebacterium glutamicum. ACS Synth Biol 4(6):729–734. CrossRefPubMedGoogle Scholar
  141. Zhou LB, Zeng AP (2015b) Engineering a lysine-ON riboswitch for metabolic control of lysine production in Corynebacterium glutamicum. ACS Synth Biol 4(12):1335–1340. CrossRefPubMedGoogle Scholar
  142. Zhou X, Rodriguez-Rivera FP, Lim HC, Bell JC, Bernhardt TG, Bertozzi CR, Theriot JA (2019) Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. Nat Chem Biol 15(3):221–231. CrossRefPubMedGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Genetics of Prokaryotes, Faculty of BiologyBielefeld UniversityBielefeldGermany
  2. 2.Center for Biotechnology (CeBiTec)Bielefeld UniversityBielefeldGermany

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