Skip to main content
Log in

The RamA regulon: complex regulatory interactions in relation to central metabolism in Corynebacterium glutamicum

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Corynebacterium glutamicum is an industrial workhorse used for the production of amino acids and a variety of other chemicals and fuels. Within its regulatory repertoire, C. glutamicum possesses RamA which was initially identified as essential transcriptional regulator of acetate metabolism. Further studies revealed its relevance for ethanol and propionate catabolism and also identified RamA to function as global regulator in the metabolism of C. glutamicum. Thereby, RamA acts as transcriptional activator or repressor of genes encoding enzymes which are involved in carbon uptake, central carbon metabolism, and cell wall synthesis. RamA controls the expression of target genes either directly and/or indirectly by constituting feed-forward loop type of transcriptional motifs with other regulators such as GlxR, SugR, RamB, and GntR1. In this review, we summarize the current knowledge on RamA, its regulon, and its regulatory interplay with other transcriptional regulators coordinating the metabolism of C. glutamicum.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alon U (2007) Network motifs: theory and experimental approaches. Nat Rev Genet 8(6):450–461

    Article  PubMed  CAS  Google Scholar 

  • Aravind L, Ponting CP (1997) The GAF domain: an evolutionary link phototransducing proteins. Trends Biochem Sci 22(12):58–59

    Article  Google Scholar 

  • Arndt A, Eikmanns BJ (2007) The alcohol dehydrogenase gene adhA in Corynebacterium glutamicum is subject to carbon catabolite repression. J Bacteriol 189(20):7408–7416

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arndt A, Auchter M, Ishige T, Wendisch VF, Eikmanns BJ (2008) Ethanol catabolism in Corynebacterium glutamicum. J Mol Microbiol Biotechnol 15(4):222–233

    Article  PubMed  CAS  Google Scholar 

  • Auchter M, Arndt A, Eikmanns BJ (2009) Dual transcriptional control of the acetaldehyde dehydrogenase gene ald of Corynebacterium glutamicum by RamA and RamB. J Biotechnol 140(1–2):84–91

    Article  PubMed  CAS  Google Scholar 

  • Auchter M, Cramer A, Hüser A, Rückert 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

    Article  PubMed  CAS  Google Scholar 

  • Blombach B, Eikmanns BJ (2011) Current knowledge on isobutanol production with Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. Bioeng Bugs 2(6):346–350

    Article  PubMed  PubMed Central  Google Scholar 

  • Blombach B, Seibold GM (2010) Carbohydrate metabolism in Corynebacterium glutamicum and applications for the metabolic engineering of L-lysine production strains. Appl Microbiol Biotechnol 86(5):1313–1322

    Article  PubMed  CAS  Google Scholar 

  • Blombach B, Schreiner ME, Bartek T, Oldiges M, Eikmanns BJ (2008) Corynebacterium glutamicum tailored for high-yield L-valine production. Appl Microbiol Biotechnol 79(3):471–479

    Article  PubMed  CAS  Google Scholar 

  • Blombach B, Arndt A, Auchter M, Eikmanns BJ (2009) L-valine production during growth of pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum in the presence of ethanol or by inactivation of the transcriptional regulator SugR. Appl Environ Microbiol 75(4):1197–1200

    Article  PubMed  CAS  Google Scholar 

  • Brinkrolf K, Schröder J, Pühler A, Tauch A (2010) The transcriptional regulatory repertoire of Corynebacterium glutamicum: reconstruction of the network controlling pathways involved in lysine and glutamate production. J Biotechnol 149(3):173–182

    Article  PubMed  CAS  Google Scholar 

  • Buchholz J, Schwentner A, Brunnenkan B, Gabris C, Grimm S, Gerstmeir R, Takors R, Eikmanns BJ, Blombach B (2013) Platform engineering of Corynebacterium glutamicum with reduced pyruvate dehydrogenase complex activity for improved production of L-lysine, L-valine, and 2-ketoisovalerate. Appl Env Microbiol 79(18):5566–5575

    Article  CAS  Google Scholar 

  • Bückle-Vallant V, Krause FS, Messerschmidt S, Eikmanns BJ (2014) Metabolic engineering of Corynebacterium glutamicum for 2-ketoisocaproate production. Appl Microbiol Biotechnol 98(1):297–311

    Article  PubMed  CAS  Google Scholar 

  • Bussmann M, Emer D, Hasenbein S, Degraf S, Eikmanns BJ, Bott M (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(3):173–182

    Article  PubMed  CAS  Google Scholar 

  • Cha PH, Park SY, Moon MW, Subhadra B, Oh TK, Kim E, Kim JF, Lee JK (2010) Characterization of an adenylate cyclase gene (cyaB) deletion mutant of Corynebacterium glutamicum ATCC 13032. Appl Microbiol Biotechnol 85(4):1061–1068

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, Zhou Y, Yang L, Chen N (2013) Modification of histidine biosynthesis pathway genes and the impact on production of L-histidine in Corynebacterium glutamicum. Biotechnol Lett 35(5):735–741

    Article  PubMed  CAS  Google Scholar 

  • Cramer A, Eikmanns BJ (2007) RamA, the transcriptional regulator of acetate metabolism in Corynebacterium glutamicum, is subject to negative autoregulation. J Mol Microbiol Biotechnol 12(1–2):51–59

    Article  PubMed  CAS  Google Scholar 

  • Cramer A, Gerstmeir R, Schaffer S, Bott M, Eikmanns BJ (2006) Identification of RamA, a novel LuxR-type transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J Bacteriol 188(7):2554–2567

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cramer A, Auchter M, Frunzke J, Bott M, Eikmanns BJ (2007) RamB, the transcriptional regulator of acetate metabolism in Corynebacterium glutamicum, is subject to regulation by RamA and RamB. J Bacteriol 189(3):1145–1149

    Article  PubMed  CAS  Google Scholar 

  • Dietrich C, Nato A, Bost B, le Maréchal P, Guyonvarch A (2009) Regulation of ldh expression during biotin-limited growth of Corynebacterium glutamicum. Microbiology 155(4):1360–1375

    Article  PubMed  CAS  Google Scholar 

  • Eggeling L, Bott M (2005) Handbook of Corynebacterium glutamicum. CRC Press, Boca Raton

    Book  Google Scholar 

  • Eggeling L, Bott M (2015) A giant market and a powerful metabolism: L-lysine provided by Corynebacterium glutamicum. Appl Microbiol Biotechnol 99(8):3387–3394

    Article  PubMed  CAS  Google Scholar 

  • Emer D, Krug A, Eikmanns BJ, Bott M (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(1–2):92–98

    Article  PubMed  CAS  Google Scholar 

  • Engels V, Wendisch VF (2007) The DeoR-type regulator SugR represses expression of ptsG in Corynebacterium glutamicum. J Bacteriol 189(8):2955–2966

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Frunzke J, Engels V, Hasenbein S, Gätgens C, Bott M (2008) Co-ordinated regulation of gluconate catabolism and glucose uptake in Corynebacterium glutamicum by two functionally equivalent transcriptional regulators, GntR1 and GntR2. Mol Microbiol 67(2):305–322

    Article  PubMed  CAS  Google Scholar 

  • Gaigalat L, Schlüter J, Hartmann M (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 15(8):104

    Article  CAS  Google Scholar 

  • Gerstmeir R, Wendisch VF, Schnicke S, Ruan H, Farwick M, Reinscheid D, Eikmanns BJ (2003) Acetate metabolism and its regulation in Corynebacterium glutamicum. J Biotechnol 104(1–3):99–122

    Article  PubMed  CAS  Google Scholar 

  • Gerstmeir R, Cramer A, Dangel P, Schaffer S, Eikmanns BJ (2004) RamB, a novel transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J Bacteriol 186(9):2798–2809

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hansmeier N, Albersmeier A, Tauch A, Damberg T, Ros R, Anselmetti D, Pühler A (2006) The surface (S)-layer gene cspB of Corynebacterium glutamicum is transcriptionally activated by a luxR-type regulator and located on a 6 kb genomic island absent from the type strain ATCC 13032. Microbiology 152:923–935

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa S, Suda M, Uematsu K, Natsuma Y, Hiraga K, Jojima T, Inui M, Yukawa H (2013) Engineering of Corynebacterium glutamicum for high-yield L-valine production under oxygen deprivation conditions. Appl Env Microbiol 79(4):1250–1257

    Article  CAS  Google Scholar 

  • Heider SAE, Wendisch VF (2015) Engineering microbial cell factories: metabolic engineering of Corynebacterium glutamicum with a focus on non-natural products. Biotechnol J 10(8):1170–1184

    Article  PubMed  CAS  Google Scholar 

  • Hüser AT, Chassagnole C, Lindley ND, Merkamm M, Guyonvarch A, Elisakova V, Patek M, Kalinowski J, Brune I, Pühler A, Tauch A (2005) Rational design of a Corynebacterium glutamicum pantothenate production strain and its characterization by metabolic flux analysis and genome-wide transcriptional profiling. Appl Env Microbiol 71(6):3255–3268

    Article  CAS  Google Scholar 

  • Inui M, Kawaguchi H, Murakami S, Vert AA (2004) Metabolic engineering of Corynebacterium glutamicum for fuel ethanol production under oxygen-deprivation conditions. J Mol Microbiol Biotechnol 8(4):243–254

    Article  PubMed  CAS  Google Scholar 

  • Joerger RD, Jacobson MR, Bishop PE (1989) Two nifA-like genes required for expression of alternative nitrogenases by Azotobacter vinelandii. J Bacteriol 171(6):3258–3267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jolkver E, Emer D, Ballan S, Krämer R, Eikmanns BJ, Marin K (2009) Identification and characterization of a bacterial transport system for the uptake of pyruvate, propionate, and acetate in Corynebacterium glutamicum. J Bacteriol 191(3):940–948

    Article  PubMed  CAS  Google Scholar 

  • Joo YC, You SK, Shin SK, Ko KH, Sim SA, Ha SO (2017) Bio-based production of dimethyl itaconate from rice wine waste-derived itaconic acid. Biotechnol J 12(11). 10.1002/biot.201700114. Epub 2017 Sep 15

  • Jungwirth B, Emer D, Brune I, Hansmeier N, Pühler A, Eikmanns BJ, Tauch A (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 cAMP-dependent regulator GlxR. FEMS Microbiol Lett 281(2):190–197

    Article  PubMed  CAS  Google Scholar 

  • Kanacher T, Schultz A, Linder JU, Schultz JE (2002) A GAF-domain-regulated adenylyl cyclase from Anabaena is a self-activating cAMP switch. EMBO J 21(14):3672–3680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaneko T, Nakamura Y, Wolk CP, Kuritz T, Sasamoto S, Watanabe A, Iriguchi M, Ishikawa A, Kawashima K, Kimura T, Kishida Y, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakazaki N, Shimpo S, Sugimoto M, Takazawa M, Yamada M, Yasuda M, Tabata S (2001) Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120. DNA Res 8(5):205–213

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Kim T, Kim Y, Lee H (2004) Identification and characterization of glxR, a gene involved in regulation of glyoxylate bypass in Corynebacterium glutamicum. J Bacteriol 186(11):3453–3460

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kimura E (2002) Triggering mechanism of L-glutamate overproduction by DtsR1 in coryneform bacteria. J Biosci Bioeng 94(6):545–551

    Article  PubMed  CAS  Google Scholar 

  • Kind S, Wittmann C (2011) Bio-based production of the platform chemical 1,5-diaminopentane. Appl Microbiol Biotechnol 91(5):1287–1296

    Article  PubMed  CAS  Google Scholar 

  • Klaffl S, Brocker M, Kalinowski J, Eikmanns BJ, Bott M (2013) Complex regulation of the phosphoenolpyruvate carboxykinase gene pck and characterization of its GntR-type regulator IolR as a repressor of myo-inositol utilization genes in Corynebacterium glutamicum. J Bacteriol 195(18):4283–4296

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kohl TA, Tauch A (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(4):239–246

    Article  PubMed  CAS  Google Scholar 

  • Kohl TA, Baumbach J, Jungwirth B, Pühler A, Tauch A (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(4):340–350

    Article  PubMed  CAS  Google Scholar 

  • Krause FS, Blombach B, Eikmanns BJ (2010) Metabolic engineering of Corynebacterium glutamicum for 2-ketoisovalerate production. Appl Env Microbiol 76(24):8053–8061

    Article  CAS  Google Scholar 

  • Krause JP, Polen T, Youn JW, Emer D, Eikmanns BJ, Wendisch VF (2012) Regulation of the malic enzyme gene malE by the transcriptional regulator MalR in Corynebacterium glutamicum. J Biotechnol 159(3):204–215

    Article  PubMed  CAS  Google Scholar 

  • Kulis-Horn RK, Persicke M, Kalinowski J (2014) Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum. Microb Biotechnol 7(1):5–25

    Article  PubMed  CAS  Google Scholar 

  • Lee SM, Lee JY, Park KJ, Park JS, Ha UH, Kim Y, Lee HS (2010) The regulator RamA influences cmytA transcription and cell morphology of Corynebacterium ammoniagenes. Curr Microbiol 61(2):92–100

    Article  PubMed  CAS  Google Scholar 

  • Letek M, Valbuena N, Ramos A, Ordóñez E, Gil JA, Mateos LM (2006) Characterization and use of catabolite-repressed promoters from gluconate genes in Corynebacterium glutamicum. J Bacteriol 188(2):409–423

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liebl W (2006) The genus Corynebacterium—nonmedical. In: Dworkin M, Falkow S, Rosenberg E, Schleifer KH, Stackebrandt E (eds) The prokaryotes, vol 3, 3rd edn. Springer, New York, pp 796–818

    Chapter  Google Scholar 

  • Lindner SN, Petrov DP, Hagmann CT, Henrich A, Krämer R, Eikmanns BJ, Wendisch VF, Seibold GM (2013) Phosphotransferase system-mediated glucose uptake is repressed in phosphoglucoisomerase-deficient Corynebacterium glutamicum strains. Appl Environ Microbiol 79(8):2588–2595

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Mangan S, Alon U (2003) Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci U S A 100(21):11980–11985

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mangan S, Itzkovitz S, Zaslaver A, Alon U (2006) The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli. J Mol Biol 356(5):1073–1081

    Article  PubMed  CAS  Google Scholar 

  • Marx A, Striegel K, de Graaf AA, Sahm H, Eggeling L (1997) Response of the central metabolism of Corynebacterium glutamicum to different flux burdens. Biotechnol Bioeng 56(2):168–180

    Article  PubMed  CAS  Google Scholar 

  • Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298(5594):824–827

    Article  PubMed  CAS  Google Scholar 

  • Mitsuhashi S, Ohnishi J, Hayashi M, Ikeda M (2004) A gene homologous to beta-type carbonic anhydrase is essential for the growth of Corynebacterium glutamicum under atmospheric conditions. Appl Microbiol Biotechnol 63(5):592–601

    Article  PubMed  CAS  Google Scholar 

  • Montgomery BL, Lagarias JC (2002) Phytochrome ancestry: sensors of bilins and light. Trends Plant Sci 7(8):357–366

    Article  PubMed  CAS  Google Scholar 

  • Moon MW, Park SY, Choi SK, Lee JK (2007) The phosphotransferase system of Corynebacterium glutamicum: features of sugar transport and carbon regulation. J Mol Microbiol Biotechnol 12(1–2):43–50

    Article  PubMed  CAS  Google Scholar 

  • Moritz B, Striegel K, Graaf AA, Sahm H (2000) Kinetic properties of the glucose-6-phosphate and 6-phosphogluconate dehydrogenases from Corynebacterium glutamicum and their application for predicting pentose phosphate pathway flux in vivo. Eur J Biochem 267(12):3442–3452

    Article  PubMed  CAS  Google Scholar 

  • Nguyen AQ, Schneider J, Reddy GK, Wendisch VF (2015) Fermentative production of the diamine putrescine: system metabolic engineering of Corynebacterium glutamicum. Meta 5(2):211–231

    CAS  Google Scholar 

  • Park SH, Kim HU, Kim TY, Park JS, Kim S, Lee SY (2014) Metabolic engineering of Corynebacterium glutamicum for L-arginine production. Nat Commun 5(4618). https://doi.org/10.1038/ncomms5618

  • Pérez-García A, Ziert C, Risse JM, Wendisch VF (2017) Improved fermentative production of the compatible solute ectoine by Corynebacterium glutamicum from glucose and alternative carbon sources. J Biotechnol 258:59–68

    Article  PubMed  CAS  Google Scholar 

  • Petri K, Walter F, Persicke M, Rückert C, Kalinowski J (2013) A novel type of N-acetylglutamate synthase is involved in the first step of arginine biosynthesis in Corynebacterium glutamicum. BMC Genomics 14:713

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reinscheid DJ, Eikmanns BJ, Sahm H (1994a) Characterization of the isocitrate lyase gene from Corynebacterium glutamicum and biochemical analysis of the enzyme. J Bacteriol 176(12):3474–3483

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reinscheid DJ, Eikmanns BJ, Sahm H (1994b) Malate synthase from Corynebacterium glutamicum: sequence analysis of the gene and biochemical characterization of the enzyme. Microbiology 140:3099–3108

    Article  PubMed  CAS  Google Scholar 

  • Reinscheid DJ, Schnicke S, Rittmann D, Zahnow U, Sahm H, Eikmanns BJ (1999) Cloning, sequence analysis, expression and inactivation of the Corynebacterium glutamicum pta-ack operon encoding phosphotransacetylase and acetate kinase. Microbiology 145(2):503–513

    Article  PubMed  CAS  Google Scholar 

  • Sakai S, Tsuchida Y, Okino S, Ichihashi O, Kawaguchi H, Watanabe T, Inui M, Yukawa H (2007) Effect of lignocellulose-derived inhibitors on growth of and ethanol production by growth-arrested Corynebacterium glutamicum R. Appl Env Microbiol 73(7):2349–2353

    Article  CAS  Google Scholar 

  • Santos CL, Correia-Neves M, Moradas-Ferreira P, Mendes MV (2012) A walk into the LuxR regulators of actinobacteria: phylogenomic distribution and functional diversity. PLoS One 7(10):e46758

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sato-nara K, Yuhashi K, Higashi K, Hosoya K, Kubota M, Ezura H (1999) Stage- and tissue-specific expression of ethylene receptor homolog genes during fruit development in muskmelon. Plant Physiol 120(1):321–330

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sauer U, Eikmanns BJ (2005) The PEP–pyruvate–oxaloacetate node as the switch point for carbon flux distribution in bacteria. FEMS Microbiol Rev 29(4):765–794

    Article  PubMed  CAS  Google Scholar 

  • Schneider J, Wendisch VF (2011) Biotechnological production of polyamines by bacteria: recent achievements and future perspectives. Appl Microbiol Biotechnol 91(1):17–30

  • Seibold GM, Hagmann CT, Schietzel M, Emer D, Auchter M, Schreiner J, Eikmanns BJ (2010) The transcriptional regulators RamA and RamB are involved in the regulation of glycogen synthesis in Corynebacterium glutamicum. Microbiology 156(4):1256–1263

    Article  PubMed  CAS  Google Scholar 

  • Shah A, Eikmanns BJ (2016) Transcriptional regulation of the β-type carbonic anhydrase gene bca by RamA in Corynebacterium glutamicum. PLoS One 11(4):e0154382

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sharrock RA, Quail PH (1989) Novel phytochrome sequences in Arabidopsis thaliana: structure, evolution, and differential expression of a plant regulatory photoreceptor family. Genes Dev 3(11):1745–1757

    Article  PubMed  CAS  Google Scholar 

  • Shen-Orr SS, Milo R, Mangan S, Alon U (2002) Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 31(1):64–68

    Article  PubMed  CAS  Google Scholar 

  • Song Y, Matsumoto K, Yamada M, Gohda A, Brigham CJ, Sinskey AJ, Taguchi S (2012) Engineered Corynebacterium glutamicum as an endotoxin-free platform strain for lactate-based polyester production. Appl Microbiol Biotechnol 93(5):1917–1925

    Article  PubMed  CAS  Google Scholar 

  • Subhadra B, Lee JK (2013) Elucidation of the regulation of ethanol catabolic genes and ptsG using a glxR and adenylate cyclase gene (cyaB) deletion mutants of Corynebacterium glutamicum ATCC 13032. J Microbiol Biotechnol 23(12):1683–1690

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y, Okai N, Teramoto H, Inui M, Yukawa H (2008a) Regulation of the expression of phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) genes in Corynebacterium glutamicum R. Microbiology 154(1):264–274

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y, Teramoto H, Inui M, Yukawa H (2008b) Regulation of expression of general components of the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) by the global regulator SugR in Corynebacterium glutamicum. Appl Microbiol Biotechnol 78(2):309–318

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y, Ehira S, Teramoto H, Inui M, Yukawa H (2012) Coordinated regulation of gnd, which encodes 6-phosphogluconate dehydrogenase, by the two transcriptional regulators GntR1 and RamA in Corynebacterium glutamicum. J Bacteriol 194(23):6527–6536

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Toyoda K, Teramoto H, Inui M, Yukawa H (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

    Article  PubMed  CAS  Google Scholar 

  • Toyoda K, Teramoto H, Inui M, Yukawa H (2009a) 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(3):968–977

    Article  PubMed  CAS  Google Scholar 

  • Toyoda K, Teramoto H, Inui M, Yukawa H (2009b) Molecular mechanism of sugar-mediated sugar-dependent expression of the ldhA gene encoding L-lactate dehydrogenase in Corynebacterium glutamicum. Appl Microbiol Biotechnol 83:315–327

    Article  PubMed  CAS  Google Scholar 

  • Toyoda K, Teramoto H, Inui M, Yukawa H (2011) Genome-wide identification of in vivo binding sites of GlxR, a cyclic AMP receptor protein-type regulator in Corynebacterium glutamicum. J Bacteriol 193(16):4123–4133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Toyoda K, Teramoto H, Gunji W, Inui M, Yukawa H (2013) Involvement of regulatory interactions among global regulators GlxR, SugR, and RamA in expression of ramA in Corynebacterium glutamicum. J Bacteriol 195(8):1718–1726

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Urao T, Yamaguchi-Shinozaki K, Shinozaki K (2001) Plant histidine kinases: an emerging picture of two-component signal transduction in hormone and environmental responses. Sci STKE (109):1–4

  • van Ooyen J, Emer D, Bussmann M, Bott M, Eikmanns BJ, Eggeling L (2011) Citrate synthase in Corynebacterium glutamicum is encoded by two gltA transcripts which are controlled by RamA, RamB, and GlxR. J Biotechnol 154(2–3):140–148

    Article  PubMed  CAS  Google Scholar 

  • Vogt M, Haas S, Polen T, Van OJ, Bott M (2015) Production of 2-ketoisocaproate with Corynebacterium glutamicum strains devoid of plasmids and heterologous genes. Microb Biotechnol 8(2):351–360

    Article  PubMed  CAS  Google Scholar 

  • Wendisch VF, de Graaf AA, Sahm H, Eikmanns BJ (2000) Quantitative determination of metabolic fluxes during coutilization of two carbon sources: comparative analyses with Corynebacterium glutamicum during growth on acetate and/or glucose. J Bacteriol 182(11):3088–3096

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wieschalka S, Blombach B, Eikmanns BJ (2012) Bio-based production of organic acids with Corynebacterium glutamicum. Microb Biotechnol 6(2):87–102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Witthoff S, Mühlroth A, Marienhagen J, Bott M (2013) C1 metabolism in Corynebacterium glutamicum: an endogenous pathway for oxidation of methanol to carbon dioxide. Appl Environ Microbiol 79(22):6974–6983

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamoto S, Suda M, Niimi S, Inui M, Yukawa H (2013) Strain optimization for efficient isobutanol production using Corynebacterium glutamicum under oxygen deprivation. Biotechnol Bioeng 110(11):2938–2948

    Article  PubMed  CAS  Google Scholar 

  • Zoraghi R, Corbin J, Francis S (2004) Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins. Mol Pharmacol 65(2):267–278

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernhard J. Eikmanns.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, A., Blombach, B., Gauttam, R. et al. The RamA regulon: complex regulatory interactions in relation to central metabolism in Corynebacterium glutamicum. Appl Microbiol Biotechnol 102, 5901–5910 (2018). https://doi.org/10.1007/s00253-018-9085-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-018-9085-3

Keywords

Navigation