한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)

  • 제38권4호
  • /
  • Pages.349-361
  • /
  • 2010
  • /
  • 1598-642X(pISSN)
  • /
  • 2234-7305(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지

Corynebacterium glutamicum의 탄소대사 및 총체적 탄소대사 조절

Carbon Metabolism and Its Global Regulation in Corynebacterium glutamicum

  • 이정기 (배재대학교 생명유전공학과)
  • Lee, Jung-Kee (Department of Life Science & Genetic Engineering, Paichai University)
  • 투고 : 2010.09.18
  • 심사 : 2010.11.05
  • 발행 : 2010.12.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

본 총설에서는 아미노산의 공업적 생산균인 Corynebacterium glutamicum의 탄소 대사 및 이와 관련된 총체적 조절 메커니즘에 대한 최근의 연구를 정리하였다. C. glutamicum의 산업적 발효을 위한 기질로서 사용되는 당밀은 주로 sucrose, glucose, fructose로 이루어져 있으며, 이들 당은 phosphotransferase system을 통해서 수송된다. C. glutamicum의 탄소 대사 특징은 glucose가 다른 당이나 유기산 등과 함께 존재할 때, glucose와 이러한 탄소원 들을 동시에 대사한다. 그러나 glucose/glutamate 혹은 glucose/ethanol 등의 혼합물에서 는 탄소원의 순차적 이용으로 인해 나타나는 diauxic growth 현상을 나타내며, 이러한 carbon catabolite repression(CCR) 현상은 E. coli나 B. subtilis 등에서 알려진 것과는 다른 독특한 분자적 메커니즘과 조절 circuits을 가지고 있음이 밝혀지고 있다. C. glutamicum의 CRP homologue인 GlxR은 acetate 대사를 포함하여 glycolysis, gluconeogenesis 및 TCA cycle 등을 포함하는 중심탄소대사 조절 뿐만 아니라, 다양한 세포 기능의 조절에 관여하는 총체적 조절 단백질로서의 역할이 제시되고 있다. C. glutamicum의 adenylate cyclase(AC)는 막과 결합된 class IIIAC 로서, 막 단백질의 특성상 아직 규명되어 있지 않은 세포 외부의 환경 변화에 대응하여 세포 내의 cAMP합성 수준을 조절할 수 있는 sensor로 추정할 수 있다. 특히 C. glutamicum의 경우 배지내 glucose 를 비롯한 탄소원과 cAMP 농도와의 관련성이 E. coli에서 알려진 교과서적 지식과는 상반되게 변화하는 경향을 보이고 있어, cAMP signaling에 의한 세포 내 regulatory network 등은 향후 풀어야 할 의문으로 남아있다. 탄소대사 조절의 최상위에 존재하며 global 조절자인 GlxRcAMP 복합체 이외에도 차상위 전사조절 단백질로서 RamB, RamA, SugR 등이 존재하여 다양한 탄소대사를 조절한다. 최근 들어서는 새로운 탄소원으로서 대두되고 있는 biomass 관련 기질들을 이용할 수 있는 C. glutamucum 균주 구축을 통하여 이용 기질의 범위를 확대시키고자 하는 연구 및 탄소 대사와 관련하여 L-lysine의 발효 수율 혹은 생산성을 향상시키고자 하는 다양한 분자적 균주 육종 연구 등이 수행되고 있다.

In this review, the current knowledge of the carbon metabolism and global carbon regulation in Corynebacterium glutamicum are summarized. C. gluamicum has phosphotransferase system (PTS) for the utilization of sucrose, glucose, and fructose. C. glutamicum does not show any preference for glucose when various sugars or organic acids are present with glucose, and thus cometabolizes glucose with other sugars or organic acids. The molecular mechanism of global carbon regulation such as carbon catabolite repression (CCR) in C. glutamicum is quite different to that in Gram-negative or low-GC Gram-positive bacteria. GlxR (glyoxylate bypass regulator) in C. glutamicum is the cyclic AMP receptor protein (CRP) homologue of E. coli. GlxR has been reported to regulate genes involved in not only glyoxylate bypass, but also central carbon metabolism and CCR including glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle. Therefore, GlxR has been suggested as a global transcriptional regulator for the regulation of diverse physiological processes as well as carbon metabolism. Adenylate cyclase of C. glutamicum is a membrane protein belonging to class III adenylate cyclases, thus it could possibly be a sensor for some external signal, thereby modulating cAMP level in response to environmental stimuli. In addition to GlxR, three additional transcriptional regulators like RamB, RamA, and SugR are also involved in regulating the expression of many genes of carbon metabolism. Finally, recent approaches for constructing new pathways for the utilization of new carbon sources, and strategies for enhancing amino acid production through genetic modification of carbon metabolism or regulatory network are described.

키워드

참고문헌

  1. Arndt, A. and B. J. Eikmanns. 2007. The alcohol dehydrogenase gene adhA in Corynebacterium glutamicum is subject to carbon catabolite repression. J. Bacteriol. 189: 7408-7416. https://doi.org/10.1128/JB.00791-07
  2. Arndt, A. and B. J. Eikmanns. 2008. Regulation of carbon metabolism in Corynebacterium glutamicum. In: Burkovski A. (ed) Corynebacteria Genomics and Molecular Biology. Caister Academic Press, Norfolk UK, pp 155-182.
  3. Arndt, A., M. Auchter, T. Ishige, V. F. Wendisch, and B. J. Eikmanns. 2008. Ethanol catabolism in Corynebacterium glutamicum. J. Mol. Microbiol. Biotechnol. 15: 222-233. https://doi.org/10.1159/000107370
  4. Auchter, M., A. Arndt, and B. J. Eikmanns. 2009. Dual transcriptional control of the acetaldehyde dehydrogenase gene ald of Corynebacterium glutamicum by RamA and RamB. J. Biotechnol. 140: 84-91. https://doi.org/10.1016/j.jbiotec.2008.10.012
  5. Auchter, M., A. Cramer, A. Hüser, C. Rückert, D. Emer, P. Schwarz, A. Arndt, C. Lange, J. Kalinowski, V. F. Wendisch, and B. J. Eikmanns. 2010. RamA and RamB are global transcriptional regulators in Corynebacterium glutamicum and control genes for enzymes of the central metabolism. J. Biotechnol. [Epub ahead of print]
  6. Bai, G., L. A. McCue, and K. A. McDonough. 2005. Characterization of Mycobacterium tuberculosis Rv3676 (CRPMt), a cyclic AMP receptor protein-like DNA binding protein. J. Bacteriol. 187: 7795-7804. https://doi.org/10.1128/JB.187.22.7795-7804.2005
  7. Barrett, E., C. Stanton, O. Zelder, G. Fitzgerald, and R. P. Ross. 2004. Heterologous expression of lactose- and galactose- utilizing pathways from lactic acid bacteria in Corynebacterium glutamicum for production of lysine in whey. J. Bacteriol. 70: 2861-2866.
  8. Becker, J., C. Klopprogge, O. Zelder, E. Heinzle, and C. Wittmann. 2005. Amplified expression of fructose 1,6-bisphosphatase in Corynebacterium glutamicum increases in vivo flux through the pentose phosphate pathway and lysine production on different carbon sources. Appl. Environ. Microbiol. 71: 8587-8596. https://doi.org/10.1128/AEM.71.12.8587-8596.2005
  9. Becker, J., C. Klopprogge, A. Herold, O. Zelder, C. J. Bolten, and C. Wittmann. 2007. Metabolic flux engineering of L-lysine production in Corynebacterium glutamicumover expression and modification of G6P dehydrogenase. J. Biotechnol. 132: 99-109. https://doi.org/10.1016/j.jbiotec.2007.05.026
  10. Becker, J., C. Klopprogge, H. Schröder, and C. Wittmann. 2009. Metabolic engineering of the tricarboxylic acid cycle for improved lysine production by Corynebacterium glutamicum. Appl. Environ. Microbiol. 75: 7866-7869. https://doi.org/10.1128/AEM.01942-09
  11. Blombach, B., M. E. Schreiner, M. Moch, M. Oldiges, and B. J. Eikmanns. 2007. Effect of pyruvate dehydrogenase complex deficiency on L-lysine production with Corynebacterium glutamicum. Appl. Microbiol. Biotechnol. 76: 615-623. https://doi.org/10.1007/s00253-007-0904-1
  12. Blombach, B., A. Cramer, B. J. Eikmanns, and M. Schreiner. 2009. RamB is an activator of the pyruvate dehydrogenase complex subunit E1p gene in Corynebacterium glutamicum. J. Mol. Microbiol. Biotechnol. 16: 236-239. https://doi.org/10.1159/000108782
  13. Blombach, B., and G. M. Seibold. 2010. Carbohydrate metabolism in Corynebacterium glutamicum and applications for the metabolic engineering of L-lysine production strains. Appl. Microbiol. Biotechnol. 86: 1313-1322. https://doi.org/10.1007/s00253-010-2537-z
  14. Bott, M. 2007. Offering surprises: TCA cycle regulation in Corynebacterium glutamicum. Trends Microbiol. 15: 417-425. https://doi.org/10.1016/j.tim.2007.08.004
  15. Brabetz, W., W. Liebl, and K. H. Schleifer. 1991. Studies on the utilization of lactose by Corynebacterium glutamicum, bearing the lactose operon of Escherichia coli. Arch. Microbiol. 155: 607-612. https://doi.org/10.1007/BF00245357
  16. Brinkrolf, K., S. Ploger, S. Solle, I. Brune, S. S. Nentwich, A. T. Hüser, J. Kalinowski, A. Puhler, and A. Tauch 2008. The LacI/GalR family transcriptional regulator UriR negatively controls uridine utilization of Corynebacterium glutamicum by binding to catabolite-responsive element (cre)-like sequences. Microbiology. 154: 1068-1081. https://doi.org/10.1099/mic.0.2007/014001-0
  17. Brinkrolf, K., J. Schroder, A. Puhler, and A. Tauch. 2010. The transcriptional regulatory repertoire of Corynebacterium glutamicum: Reconstruction of the network controlling pathways involved in lysine and glutamate production. J. Biotechnol. 149: 173-182. https://doi.org/10.1016/j.jbiotec.2009.12.004
  18. Bruckner, R. and F. Titgemeyer. 2002. Carbon catabolite repression in bacteria: choice of the carbon source and autoregulatory limitation of sugar utilization. FEMS Microbiol. Lett. 209: 141-148.
  19. Brune, I, K. Brinkrolf, J. Kalinowski, A. Pühler, and A. Tauch. 2005. The individual and common repertoire of DNA-binding transcriptional regulators of Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium diphtheriae and Corynebacterium jeikeium deduced from the complete genome sequences. BMC Genomics. 6: 86. https://doi.org/10.1186/1471-2164-6-86
  20. Bussmann, M., D. Emer, S. Hasenbein, S. Degraf, B. J. Eikmanns, and M. Bott. 2009. Transcriptional control of the succinate dehydrogenase operon sdhCAB of Corynebacterium glutamicum by the cAMP-dependent regulator GlxR and the LuxR-type regulator RamA. J. Biotechnol. 143: 173-182. https://doi.org/10.1016/j.jbiotec.2009.06.025
  21. Cha, P. H., S. Y. Park, M. W. Moon, B. Subhadra, T. K. Oh, E. Kim, J. F. Kim, and J. K. Lee. 2010. Characterization of an adenylate cyclase gene (cyaB) deletion mutant of Corynebacterium glutamicum ATCC 13032. Appl. Microbiol. Biotechnol. 85: 1061-1068. https://doi.org/10.1007/s00253-009-2066-9
  22. Cocaign-Bousquet, M., A. Guyonvarch, and N. D. Lindley. 1996. Growth rate-dependenct modulation of carbon flux through central metabolism and the kinetic consequences for glucose-limited chemostat cultures of Corynebacterium glutamicum. Appl. Environ. Microbiol. 62: 429-436.
  23. Cramer A, R. Gerstmeir, S. Schaffer, M. Bott and B. J. Eikmanns. 2006. Identification of RamA, a novel LuxRtype transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J. Bacteriol. 188: 2554-2567. https://doi.org/10.1128/JB.188.7.2554-2567.2006
  24. Derouaux, A., D. Dehareng, E. Lecocq, S. Halici, H. Nothaft, F. Giannotta, G. Moutzourelis, J. Dusart, B. Devreese, F. Titgemeyer, J. Van Beeumen, and S. Rigali. 2004. Crp of Streptomyces coelicolor is the third transcription factor of the large CRP-FNR superfamily able to bind cAMP. Biochem. Biophys. Res. Commun. 325: 983-990. https://doi.org/10.1016/j.bbrc.2004.10.143
  25. Dominguez, H. and N. D. Lindley. 1996. Complete sucrose metabolism requires fructose phosphotransferase activity in Corynebacterium glutamicum to ensure phosphorylation of liberated fructose. Appl. Environ. Microbiol. 62: 3878-3880.
  26. Dominguez, H., C. Rollin, A. Guyonvarch, J. L. Guerquin- Kern, M. Cocaign-Bousquet, and N. D. Lindley. 1998. Carbon-flux distribution in the central metabolic pathways of Corynebacterium glutamicum during growth on fructose. Eur. J. Biochem. 254: 96-102. https://doi.org/10.1046/j.1432-1327.1998.2540096.x
  27. Eikmanns, B. 2004. Central metabolism: Tricarboxylic acid cycle and anaplerotic reactions. Handbook of Corynebacterium glutamicum (Eggeling L & Bott M, eds), pp. 241- 276. Taylor & Francis Group, Boca Raton, FL.
  28. Emer, D., A. Krug, B. J. Eikmanns, and M. Bott. 2009. Complex expression control of the Corynebacterium glutamicum aconitase gene: identification of RamA as a third transcriptional regulator besides AcnR and RipA. J. Biotechnol. 140: 92-98. https://doi.org/10.1016/j.jbiotec.2008.11.003
  29. Engels, V., and V. F. Wendisch. 2007. The DeoR-type regulator SugR represses expression of ptsG in Corynebacterium glutamicum. J. Bacteriol. 189: 2955-2966. https://doi.org/10.1128/JB.01596-06
  30. Gaigalat, L., J. P. Schluter, M. Hartmann, S. Mormann, A. Tauch, A. Puhler, and J. Kalinowski. 2007. The DeoR-type transcriptional regulator SugR acts as a repressor for genes encoding the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in Corynebacterium glutamicum. BMC Mol. Biol. 8: 104. https://doi.org/10.1186/1471-2199-8-104
  31. Gao, Y.G, H. Suzuki, H. Itou, Y. Zhou, Y. Tanaka, M. Wachi, N. Watanabe, I. Tanaka, and M. Yao. 2008. Structural and functional characterization of the LldR from Corynebacterium glutamicum: a transcriptional repressor involved in L-lactate and sugar utilization. Nucleic Acids Res. 36: 7110-7123. https://doi.org/10.1093/nar/gkn827
  32. Georgi, T., D. Rittmann, and V. F. Wendisch. 2005. Lysine and glutamate production by Corynebacterium glutamicum on glucose, fructose and sucrose: roles of malic enzyme and fructose-1,6-bisphosphatase. Metab. Eng. 7: 291-301. https://doi.org/10.1016/j.ymben.2005.05.001
  33. Gerstmeir, R., V. F. Wendisch, S. Schnicke, H. Ruan, M. Farwick, D. Reinscheid, and B. J. Eikmanns. 2003. Acetate metabolism and its regulation in Corynebacterium glutamicum. J. Biotechnol. 104: 99-122. https://doi.org/10.1016/S0168-1656(03)00167-6
  34. Gerstmeir R, A. Cramer, P. Dangel, S. Schaffer, and B. J. Eikmanns. 2004. RamB, a novel transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J. Bacteriol. 186: 2798-2809. https://doi.org/10.1128/JB.186.9.2798-2809.2004
  35. Gourdon, P., M. Raherimandimby, H. Dominguez, M. Cocaign-Bousquet, and N. D. Lindley. 2003. Osmotic stress, glucose transport capacity and consequences for glutamate overproduction in Corynebacterium glutamicum. J. Biotechnol. 104:77-85. https://doi.org/10.1016/S0168-1656(03)00165-2
  36. Han, S. O., M. Inui, and H. Yukawa. 2007. Expression of Corynebacterium glutamicum glycolytic genes varies with carbon source and growth phase. Microbiology. 153: 2190-2202. https://doi.org/10.1099/mic.0.2006/004366-0
  37. Han, S. O., M. Inui and H. Yukawa. 2008. Effect of carbon source availability and growth phase on expression of Corynebacterium glutamicum genes involved in the tricarboxylic acid cycle and glyoxylate bypass. Microbiology. 154: 3073-3083. https://doi.org/10.1099/mic.0.2008/019828-0
  38. Hayashi, M., H. Mizoguchi, N. Shiraishi, M. Obayashi, S. Nakagawa, J. Imai, S. Watanabe, T. Ota, and M. Ikeda. 2002. Transcriptome analysis of acetate metabolism in Corynebacterium glutamicum using a newly developed metabolic array. Biosci. Biotechnol. Biochem. 66: 1337-1344. https://doi.org/10.1271/bbb.66.1337
  39. Hvorup, R., A. B. Chang, and M. H. Saier Jr. 2003. Bioinformatic analyses of the bacterial L-ascorbate phosphotransferase system permease family. J. Mol. Microbiol. Biotechnol. 6: 191-205. https://doi.org/10.1159/000077250
  40. Ikeda, M. 2003. Amino acid production processes. Adv. Biochem. Eng. Biotechnol. 79: 2-35.
  41. Ikeda M., and S. Nakagawa. 2003. The Corynebacterium glutamicum genome: features and impacts on biotechnological processes. Appl. Micorbiol. Biotechnol. 62: 99-109. https://doi.org/10.1007/s00253-003-1328-1
  42. Ikeda, M., J. Ohnishi, M. Hayashi, and S. Mitsuhashi. 2006. A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production. J. Ind. Microbiol. Biotechnol. 33: 610-615. https://doi.org/10.1007/s10295-006-0104-5
  43. Inui, M., H. Kawaguchi, S. Murakami, A. A. Vertès, and H. Yukawa. 2004. Metabolic engineering of Corynebacterium glutamicum for fuel ethanol production under oxygendeprivation conditions. J. Mol. Microbiol. Biotechnol. 8: 243-254. https://doi.org/10.1159/000086705
  44. Jojima, T., C. A. Omumasaba, M. Inui, and H. Yukawa. 2010. Sugar transporters in efficient utilization of mixed sugar substrates: current knowledge and outlook. Appl. Microbiol. Biotechnol. 85: 471-480. https://doi.org/10.1007/s00253-009-2292-1
  45. Jolkver, E., D. Emer, S. Ballan, R. Kramer, B. J. Eikmanns, and K. Marin. 2009. Identification and characterization of a bacterial transport system for the uptake of pyruvate, propionate, and acetate in Corynebacterium glutamicum. J. Bacteriol. 191: 940-948. https://doi.org/10.1128/JB.01155-08
  46. Jungwirth B, D. Emer, I. Brune, N. Hansmeier, A. Pühler, B. J. Eikmanns, and A. Tauch. 2008. Triple transcriptional control of the resuscitation promoting factor 2 (rpf2) gene of Corynebacterium glutamicum by the regulators of acetate metabolism RamA and RamB and the cAMPdependent regulator GlxR. FEMS Microbiol. Lett. 281: 190-197. https://doi.org/10.1111/j.1574-6968.2008.01098.x
  47. Kabus, A., T. Georgi, V. F. Wendisch, and M. Bott. 2007. Expression of the Escherichia coli pntAB genes encoding a membrane-bound transhydrogenase in Corynebacterium glutamicum improves L-lysine formation. Appl. Microbiol. Biotechnol. 75: 47-53. https://doi.org/10.1007/s00253-006-0804-9
  48. Kalinowski, J., B. Bathe, D. Bartels, N. Bischoff, M. Bott, A. Burkovski, N. Dusch, L. Eggeling, B. J. Eikmanns, L. Gaigalat, A. Goesmann, M. Hartmann, K. Huthmacher, R. Kramer, B. Linke, A. C. McHardy, F. Meyer, B. Mockel, W. Pfefferle, A. Puhler, D. A. Rey, C. Ruckert, O. Rupp, H. Sahm, V. F. Wendisch, I. Wiegrabe, and A. Tauch. 2003. The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of Laspartate- derived amino acids and vitamins. J. Biotechnol. 104: 5-25. https://doi.org/10.1016/S0168-1656(03)00154-8
  49. Kawaguchi, H., A. A. Vertes, S. Okino, M. Inui, and H. Yukawa. 2006. Engineering of a xylose metabolic pathway in Corynebacterium glutamicum. Appl. Environ. Microbiol. 72: 3418-3428. https://doi.org/10.1128/AEM.72.5.3418-3428.2006
  50. Kawaguchi, H., M. Sasaki, A. A. Vertes, M. Inui, and H. Yukawa. 2008. Engineering of an L-arabinose metabolic pathway in Corynebacterium glutamicum. Appl. Microbiol. Biotechnol. 77: 1053-1062. https://doi.org/10.1007/s00253-007-1244-x
  51. Kawaguchi, H., M. Sasaki, A. A. Vertès, M. Inui, and H. Yukawa. 2009. Identification and functional analysis of the gene cluster for L-arabinose utilization in Corynebacterium glutamicum. Appl. Environ. Microbiol. 75: 3419-3429. https://doi.org/10.1128/AEM.02912-08
  52. Kim, H. J., T. H. Kim, Y. Kim, and H. S. Lee. 2004. Identification and characterization of glxR, a gene involved in regulation of glyoxylate bypass in Corynebacterium glutamicum. J. Bacteriol. 186:3453-3460. https://doi.org/10.1128/JB.186.11.3453-3460.2004
  53. Kinoshita, S., S. Udaka, and M. Shimono. 1957. Studies on the amino acid fermentation part.1. Production of L-glutamic acid by various microorganisms. J. Gen. Appl. Microbiol. 3: 193-205. https://doi.org/10.2323/jgam.3.193
  54. Koffas, M. A., G. Y. Jung, and G. Stephanopoulos. 2003. Engineering metabolism and product formation in Corynebacterium glutamicum by coordinated gene overexpression. Metab. Eng. 5: 32-41. https://doi.org/10.1016/S1096-7176(03)00002-8
  55. Kohl, T. A., J. Baumbach, B. Jungwirth, A. Puhler, and A. Tauch. 2008. The GlxR regulon of the amino acid producer Corynebacterium glutamicum: in silico and in vitro detection of DNA binding sites of a global transcription regulator. J. Biotechnol. 135: 340-350. https://doi.org/10.1016/j.jbiotec.2008.05.011
  56. Kohl, T. A. and A. Tauch. 2009. The GlxR regulon of the amino acid producer Corynebacterium glutamicum: Detection of the corynebacterial core regulon and integration into the transcriptional regulatory network model. J. Biotechnol. 143: 239-246. https://doi.org/10.1016/j.jbiotec.2009.08.005
  57. Kotrba, P., M. Inui, and H. Yukawa. 2003. A single V317A or V317M substitution in Enzyme II of a newly identified $\beta-glucoside$ phosphotransferase and utilization system of Corynebacterium glutamicum R extends its specificity towards cellobiose. Microbiology. 149: 1569-80. https://doi.org/10.1099/mic.0.26053-0
  58. Kotrbova-Kozak, A., P. Kotrba, M. Inui, J. Sajdok, and H. Yukawa. 2007. Transcriptionally regulated adhA gene encodes alcohol dehydrogenase required for ethanol and npropanol utilization in Corynebacterium glutamicum. Appl. Microbiol. Biotechnol. 76: 1347-1356. https://doi.org/10.1007/s00253-007-1094-6
  59. Kramer, R. and C. Lambert. 1990. Uptake of glutamate in Corynebacterium glutamicum. 2. Evidence for a primary active transport system. Eur. J. Biochem. 194: 937-944. https://doi.org/10.1111/j.1432-1033.1990.tb19489.x
  60. Kronemeyer, W., N. Peekhaus, R. Kramer, H. Sahm, and L. Eggeling. 1995. Structure of the gluABCD cluster encoding the glutamate uptake system of Corynebacterium glutamicum. J. Bacteriol. 177: 1152-1158.
  61. Lee, J. K., M. H. Sung, K. H. Yoon, J. H. Yu, and T. K. Oh. 1994. Nucleotide sequence of the gene encoding the Corynebacterium glutamicum mannose enzyme II and analyses of the deduced protein sequence. FEMS Microbiol. Lett. 119:137-145.
  62. Letek, M., N. Valbuena, A. Ramos, E. Ordonez, J. A. Gil, and L. M. Mateos. 2006. Characterization and use of catabolite-repressed promoters from gluconate genes in Corynebacterium glutamicum. J. Bacteriol. 188: 409-423. https://doi.org/10.1128/JB.188.2.409-423.2006
  63. Linder, J. U. 2006. Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation. Cell Mol. Life. Sci. 63: 1736-1751. https://doi.org/10.1007/s00018-006-6072-0
  64. Lindner, S. N., H. Niederholtmeyer, K. Schmitz, S. M. Schoberth, and V. F. Wendisch. 2010. Polyphosphate/ATPdependent NAD kinase of Corynebacterium glutamicum: biochemical properties and impact of ppnK overexpression on lysine production. Appl. Microbiol. Biotechnol. 87: 583-593. https://doi.org/10.1007/s00253-010-2481-y
  65. Marx, A., S. Hans, B. Möckel, B. Bathe, A. A. de Graaf, A. C. McCormack, C. Stapleton, K. Burke, M. O'Donohue, and L. K. Dunican. 2003. Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum. J. Biotechnol. 104: 185-197. https://doi.org/10.1016/S0168-1656(03)00153-6
  66. Mitsuhashi, S., M. Hayashi, J. Ohnishi, and M. Ikeda. 2006. Disruption of malate:quinone oxidoreductase increases L-lysine production by Corynebacterium glutamicum. Biosci. Biotechnol. Biochem. 70: 2803-2806. https://doi.org/10.1271/bbb.60298
  67. Moon, M.W., H. J. Kim, T. K. Oh, C. S. Shin, J. S. Lee, S. J. Kim, and J. K. Lee. 2005. Analyses of enzyme II gene mutants for sugar transport and heterologous expression of fructokinase gene in Corynebacterium glutamicum ATCC13032. FEMS Microbiol. Lett. 244:259-266. https://doi.org/10.1016/j.femsle.2005.01.053
  68. Moon, M. W, S. Y. Park, S. K. Choi and J. K. Lee. 2007. The phosphotransferase system of Corynebacterium glutamicum: features of sugar transport and carbon regulation. J. Mol. Microbiol. Biotechnol. 12: 43-50. https://doi.org/10.1159/000096458
  69. Nentwich, S. S., K. Brinkrolf, L. Gaigalat, A. T. Hüser, D. A. Rey, T. Mohrbach, K. Marin, A. Pühler, A. Tauch, and J. Kalinowski. 2009. Characterization of the LacI-type transcriptional repressor RbsR controlling ribose transport in Corynebacterium glutamicum ATCC 13032. Microbiology. 155: 150-164. https://doi.org/10.1099/mic.0.020388-0
  70. Ohnishi J., S. Mitsuhashi, M. Hayashi, S. Ando, H. Yokoi, K. Ochiai, and M. Ikeda 2002. A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant. Appl. Micorbiol. Biotechnol. 58: 217-223. https://doi.org/10.1007/s00253-001-0883-6
  71. Ohnishi, J., R. Katahira, S. Mitsuhashi, S. Kakita, and M. Ikeda. 2005. A novel gnd mutation leading to increased Llysine production in Corynebacterium glutamicum. FEMS Microbiol. Lett. 242: 265-274. https://doi.org/10.1016/j.femsle.2004.11.014
  72. Okino, S., R. Noburyu, M. Suda, T. Jojima, M. Inui, and H. Yukawa. 2008. An efficient succinic acid prodiction process in a metabolically engineered Corynebacterium glutamicum strain. J. Appl. Microbiol. Biotechnol. 81: 459-464. https://doi.org/10.1007/s00253-008-1668-y
  73. Parche, S., H. Nothaft, A. Kamionka, and F. Titgemeyer. 2000. Sugar uptake and utilisation in Streptomyces coelicolor: a PTS view to the genome. Antonie Van Leeuwenhoek. 78: 243-251. https://doi.org/10.1023/A:1010274317363
  74. Park, S. Y., H. K Kim, S. K. Yoo, T. K. Oh, and J. K. Lee. 2000. Characterization of glk, a gene coding for glucose kinase of Corynebacterium glutamicum. FEMS Microbiol. Lett. 188: 209-215. https://doi.org/10.1111/j.1574-6968.2000.tb09195.x
  75. Park, S. Y., M. W. Moon, B. D. Subhadra, and J. K. Lee 2010. Functional characterization of glxR deletion mutant of Corynebacterium glutamicum ATCC 13032: involvement of GlxR in acetate metabolism and carbon catabolite repression. FEMS Microbiol. Lett. 304: 107-115. https://doi.org/10.1111/j.1574-6968.2009.01884.x
  76. Rickman, L., C. Scott, D. M. Hunt, T. Hutchinson, M. C. Menéndez, R. Whalan, J. Hinds, M. J. Colston, J. Green, and R. S. Buxton. 2005. A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol. Microbiol. 56: 1274-1286. https://doi.org/10.1111/j.1365-2958.2005.04609.x
  77. Rittmann, D., S. N. Lindner, and V. F. Wendisch. 2008. Engineering of a glycerol utilization pathway for amino acid production by Corynebacterium glutamicum. Appl. Environ. Microbiol. 74: 6216-6222. https://doi.org/10.1128/AEM.00963-08
  78. Saier, M. H. Jr. 1989. Protein phosphorylation and allosteric control of inducer exclusion and catabolite repression by the bacterial phosphoenolpyruvate:sugar phosphotransferase system. Microbiol. Rev. 53: 109-120.
  79. Saier, M. H. Jr. 1993. Regulatory interactions involving the proteins of the phosphotransferase system in enteric bacteria. J. Cell Biochem. 51: 62-68. https://doi.org/10.1002/jcb.240510112
  80. Sasaki, M., T. Jojima, H. Kawaguchi, M. Inui, and H. Yukawa. 2009. Engineering of pentose transport in Corynebacterium glutamicum to improve simultaneous utilization of mixed sugars. Appl. Microbiol. Biotechnol. 85: 105-115. https://doi.org/10.1007/s00253-009-2065-x
  81. Schneider, J., K. Niermann, and V. F. Wendisch. 2010. Production of the amino acids L-glutamate, L-lysine, Lornithine and L-arginine from arabinose by recombinant Corynebacterium glutamicum. J. Biotechnol. [Epub ahead of print]
  82. Schroder, J., and A. Tauch. 2009. Transcriptional regulation of gene expression in Corynebacterium glutamicum: the role of global, master and local regulators in the modular and hierarchical gene regulatory network. FEMS Microbiol. Rev. 34: 685-737.
  83. Schultz, C., A. Niebisch, A. Schwaiger, U. Viets, S. Metzger, M. Bramkamp, and M. Bott. Genetic and biochemical analysis of the serine/threonine protein kinases PknA, PknB, PknG and PknL of Corynebacterium glutamicum: evidence for non-essentiality and for phosphorylation of OdhI and FtsZ by multiple kinases. Mol. Microbiol. 74: 724-741.
  84. Seibold, G., M. Auchter, S. Berens, J. Kalinowski, and B. J. Eikmanns. 2006. Utilization of soluble starch by a recombinant Corynebacterium glutamicum strain: growth and lysine production. J. Biotechnol. 124: 381-391. https://doi.org/10.1016/j.jbiotec.2005.12.027
  85. Seibold, G. M., M. Wurst, and B. J. Eikmanns. 2009. Roles of maltodextrin and glycogen phosphorylases in maltose utilization and glycogen metabolism in Corynebacterium glutamicum. Microbiology. 155: 347-358. https://doi.org/10.1099/mic.0.023614-0
  86. Seibold, G. M., C. Hagmann, M. Schiezel, D. Emer, M. Auchter, J. Schreiner, and B. J. Eikmanns. 2010. The transcriptional regulators RamA and RamB are involved in the regulation of glycogen synthesis in Corynebacterium glutamicum. Microbiology. 156: 1256-1263. https://doi.org/10.1099/mic.0.036756-0
  87. Shenoy, A. R., K. Sivakumar, A. Krupa, N. Srinivasan, and S. S. Visweswariah. 2004. A survey of nucleotide cyclases in actinobacteria: unique domain organization and expansion of the class III cyclase family in Mycobacterium tuberculosis. Comp. Funct. Genomics. 5: 17-38. https://doi.org/10.1002/cfg.349
  88. Sindelar G, and V. F Wendisch. 2007. Improving lysine production by Corynebacterium glutamicum through DNA microarray-based identification of novel target genes. Appl. Microbiol. Biotechnol 76: 677-689. https://doi.org/10.1007/s00253-007-0916-x
  89. Stansen, C., D. Uy, S. Delaunay, L. Eggeling, J. L. Goergen, and V. F. Wendisch. 2005. Characterization of a Corynebacterium glutamicum lactate utilization operon induced during temperature-triggered glutamate production. Appl. Environ. Microbiol. 71: 5920-5928. https://doi.org/10.1128/AEM.71.10.5920-5928.2005
  90. Tanaka, Y., H. Teramoto, M. Inui, and H. Yukawa. 2009. Identification of a second $\beta-glucoside$ phosphoenolpyruvate: carbohydrate phosphotransferase system in Corynebacterium glutamicum R. Microbiology. 155: 3652-3660. https://doi.org/10.1099/mic.0.029496-0
  91. Tateno, T., H. Fukuda, and A. Kondo. 2007. Production of L-Lysine from starch by Corynebacterium glutamicum displaying alpha-amylase on its cell surface. Appl. Microbiol. Biotechnol. 74: 1213-1220. https://doi.org/10.1007/s00253-006-0766-y
  92. Tateno, T., H. Fukuda, and A. Kondo. 2007. Direct production of L-lysine from raw corn starch by Corynebacterium glutamicum secreting Streptococcus bovis $\alpha-amylase$ using cspB promoter and signal sequence. Appl. Microbiol. Biotechnol. 77: 533-541. https://doi.org/10.1007/s00253-007-1191-6
  93. Titgemeyer, F., J. Amon, S. Parche, M. Mahfoud, J. Bail, M. Schlicht, N. Rehm, D. Hillmann, J. Stephan, B. Walter, A. Burkovski, and M. Niederweis. 2007. A genomic view of sugar transport in Mycobacterium smegmatis and Mycobacterium tuberculosis. J. Bacteriol. 189: 5903-5915. https://doi.org/10.1128/JB.00257-07
  94. Toyoda, K., H. Teramoto, M. Inui, and H. Yukawa. 2008. Expression of the gapA gene encoding glyceraldehyde-3- phosphate dehydrogenase of Corynebacterium glutamicum is regulated by the global regulator SugR. Appl. Microbiol. Biotechnol. 81: 291-301. https://doi.org/10.1007/s00253-008-1682-0
  95. Toyoda, K., H. Teramoto, M. Inui, and H. Yukawa. 2009. Molecular mechanism of SugR-mediated sugar-dependent expression of the ldhA gene encoding L-lactate dehydrogenase in Corynebacterium glutamicum. Appl. Microbiol. Biotechnol. 83: 315-327. https://doi.org/10.1007/s00253-009-1887-x
  96. Toyoda, K., H. Teramoto, M. Inui, and H. Yukawa. 2009. Involvement of the LuxR-type transcriptional regulator RamA in regulation of expression of the gapA gene, encoding glyceraldehyde-3-phosphate dehydrogenase of Corynebacterium glutamicum. J. Bacteriol. 191: 968-977. https://doi.org/10.1128/JB.01425-08
  97. van Ooyen, J., D. Emer, M. Bussmann, M. Bott, B. J. Eikmanns, and L. Eggeling. 2010. Citrate synthase in Corynebacterium glutamicum is encoded by two gltA transcripts which are controlled by RamA, RamB, and GlxR. J. Biotechnol. [Epub ahead of print]
  98. Wendisch, V. F., A. A. de Graaf, H. Sahm, and B. J. Eikmanns. 2000. Quantitative determination of metabolic flux during coutilization of two carbon source: comparative analyses with Corynebacterium glutamicum during growth on acetate and/or glucose. J. Bacteriol. 182:3088-3096. https://doi.org/10.1128/JB.182.11.3088-3096.2000
  99. Wendisch, V. F., M. Bott, J. Kalinowski, M. Oldiges, and W. Wiechert. 2006. Emerging Corynebacterium glutamicum systems biology. J. Biotechnol. 124: 74-92. https://doi.org/10.1016/j.jbiotec.2005.12.002
  100. Wendisch V. F. 2006. Genetic Regulation of Corynebacterium glutamicum Metabolism. J. Microbiol. Biotechnol. 16: 999-1009.