Abstract
The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTSGlc) is the major uptake system responsible for transporting glucose, and is involved in glucose translocation and phosphorylation in Corynebacterium glutamicum. For the longest time, the PTSGlc was considered as the only uptake system for glucose. However, some PTS-independent glucose uptake systems (non-PTSGlc) were discovered in recent years, such as the coupling system of inositol permeases and glucokinases (IPGS) and the coupling system of β-glucoside-PTS permease and glucokinases (GPGS). The products (e.g. lysine, phenylalanine and leucine) will be increased because of the increasing intracellular level of phosphoenolpyruvate (PEP), while some by-products (e.g. lactic acid, alanine and acetic acid) will be reduced when this system become the main uptake pathway for glucose. In this review, we survey the uptake systems for glucose in C. glutamicum and their composition. Furthermore, we summarize the latest research of the regulatory mechanisms among these glucose uptake systems. Detailed strategies to manipulate glucose uptake system are addressed based on this knowledge.
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References
Aboulwafa M, Saier MH Jr (2002) Dependency of sugar transport and phosphorylation by the phosphoenolpyruvate-dependent phosphotransferase system on membranous phosphatidyl glycerol in Escherichia coli: studies with a pgsA mutant lacking phosphatidyl glycerophosphate synthase. Res Microbiol 153:667–677. https://doi.org/10.1016/s0923-2508(02)01376-1
Becker J, Zelder O, Hafner S, Schroder H, Wittmann C (2011) From zero to hero–design-based systems metabolic engineering of Corynebacterium glutamicum for l-lysine production. Metab Eng 13:159–168. https://doi.org/10.1016/j.ymben.2011.01.003
Blombach B, Seibold GM (2010) Carbohydrate metabolism in Corynebacterium glutamicum and applications for the metabolic engineering of l-lysine production strains. Appl Microbiol Biotechnol 86:1313–1322. https://doi.org/10.1007/s00253-010-2537-z
Brusseler C, Radek A, Tenhaef N, Krumbach K, Noack S, Marienhagen J (2018) The myo-inositol/proton symporter IolT1 contributes to d-xylose uptake in Corynebacterium glutamicum. Bioresour Technol 249:953–961. https://doi.org/10.1016/j.biortech.2017.10.098
Chen Q, Amster-Choder O (1998) The different functions of BglF, the E. coli beta-glucoside permease and sensor of the bgl system, have different structural requirements. Biochemistry US 37:17040–17047. https://doi.org/10.1021/bi980067n
Cote CK, Cvitkovitch D, Bleiweis AS, Honeyman AL (2000) A novel beta-glucoside-specific PTS locus from Streptococcus mutans that is not inhibited by glucose. Microbiology 146(Pt 7):1555–1563. https://doi.org/10.1099/00221287-146-7-1555
Engels V, Wendisch VF (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
Engels V, Lindner SN, Wendisch VF (2008) The global repressor SugR controls expression of genes of glycolytic and of the L-lactate dehydrogenase LdhA in Corynebacterium glutamicum. J Bacteriol 190:8033–8044. https://doi.org/10.1128/JB.00705-08
Frunzke J, Engels V, Hasenbein S, Gatgens 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 67:305–322. https://doi.org/10.1111/j.1365-2958.2007.06020.x
Gaigalat L, Schluter JP, Hartmann M, Mormann S, Tauch A, Puhler A, Kalinowski J (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
Henrich A, Kuhlmann N, Eck AW, Kramer R, Seibold GM (2013) Maltose uptake by the novel ABC transport system MusEFGK2I causes increased expression of ptsG in Corynebacterium glutamicum. J Bacteriol 195:2573–2584. https://doi.org/10.1128/jb.01629-12
Ikeda M (2012) Sugar transport systems in Corynebacterium glutamicum: features and applications to strain development. Appl Microbiol Biotechnol 96:1191–1200. https://doi.org/10.1007/s00253-012-4488-z
Ikeda M, Mizuno Y, Awane S, Hayashi M, Mitsuhashi S, Takeno S (2011) Identification and application of a different glucose uptake system that functions as an alternative to the phosphotransferase system in Corynebacterium glutamicum. Appl Microbiol Biotechnol 90:1443–1451. https://doi.org/10.1007/s00253-011-3210-x
Ikeda M, Noguchi N, Ohshita M, Senoo A, Mitsuhashi S, Takeno S (2015) A third glucose uptake bypass in Corynebacterium glutamicum ATCC 31833. Appl Microbiol Biotechnol 99:2741–2750. https://doi.org/10.1007/s00253-014-6323-1
Kalebina TS, Egorov SN, Arbatskii NP, Bezsonov EE, Gorkovskii AA, Kulaev IS (2008) The role of high-molecular-weight polyphosphates in activation of glucan transferase Bgl2p from Saccharomyces cerevisiae cell wall. Doklady Biochem Biophys 420:142–145. https://doi.org/10.1134/s1607672908030125
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 195:4283–4296. https://doi.org/10.1128/JB.00265-13
Kotrba P, Inui M, Yukawa H (2001a) Bacterial phosphotransferase system (PTS) in carbohydrate uptake and control of carbon metabolism. J Biosci Bioeng 92:502–517. https://doi.org/10.1263/jbb.92.502
Kotrba P, Inui M, Yukawa H (2001b) The ptsI gene encoding enzyme I of the phosphotransferase system of Corynebacterium glutamicum. Biochem Biophys Res Commun 289:1307–1313. https://doi.org/10.1006/bbrc.2001.6116
Kotrba P, Inui M, Yukawa H (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 149:1569–1580. https://doi.org/10.1099/mic.0.26053-0
Krause FS, Henrich A, Blombach B, Kramer R, Eikmanns BJ, Seibold GM (2010) Increased glucose utilization in Corynebacterium glutamicum by use of maltose, and its application for the improvement of l-valine productivity. Appl Environ Microbiol 76:370–374. https://doi.org/10.1128/aem.01553-09
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 188:8054–8061. https://doi.org/10.1128/jb.00935-06
Kumar S, Narayan KS, Shandilya S, Sood SK, Kapila S (2019) Role of non-PTS dependent glucose permease (GlcU) in maintaining the fitness cost during acquisition of nisin resistance by Enterococcus faecalis. Fems Microbiol Lett. https://doi.org/10.1093/femsle/fnz230
Lambrecht SJ, Wahlig JML, Steglich C (2018) The GntR family transcriptional regulator PMM1637 regulates the highly conserved cyanobacterial sRNA Yfr2 in marine picocyanobacteria. DNA Res 25:489–497. https://doi.org/10.1093/dnares/dsy019
Lara AR, Caspeta L, Gosset G, Bolivar F, Ramirez OT (2008) Utility of an Escherichia coli strain engineered in the substrate uptake system for improved culture performance at high glucose and cell concentrations: an alternative to fed-batch cultures. Biotechnol Bioeng 99:893–901. https://doi.org/10.1002/bit.21664
Lee JK, Sung MH, Yoon KH, Yu JH, Oh TK (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. https://doi.org/10.1111/j.1574-6968.1994.tb06880.x
Lindner SN, Knebel S, Pallerla SR, Schoberth SM, Wendisch VF (2010) Cg2091 encodes a polyphosphate/ATP-dependent glucokinase of Corynebacterium glutamicum. Appl Microbiol Biotechnol 87:703–713. https://doi.org/10.1007/s00253-010-2568-5
Lindner SN, Seibold GM, Henrich A, Kramer R, Wendisch VF (2011) Phosphotransferase system-independent glucose utilization in Corynebacterium glutamicum by inositol permeases and glucokinases. Appl Environ Microbiol 77:3571–3581. https://doi.org/10.1128/AEM.02713-10
Lindner SN et al (2013) Phosphotransferase system-mediated glucose uptake is repressed in phosphoglucoisomerase-deficient Corynebacterium glutamicum strains. Appl Environ Microbiol 79:2588–2595. https://doi.org/10.1128/aem.03231-12
Liu L, Duan X, Wu J (2016) Modulating the direction of carbon flow in Escherichia coli to improve l-tryptophan production by inactivating the global regulator FruR. J Biotechnol 231:141–148. https://doi.org/10.1016/j.jbiotec.2016.06.008
Liu L, Chen S, Wu J (2017) Phosphoenolpyruvate:glucose phosphotransferase system modification increases the conversion rate during l-tryptophan production in Escherichia coli. J Ind Microbiol Biotechnol 44:1385–1395. https://doi.org/10.1007/s10295-017-1959-3
Michiko M, Shiio I (1987) Phosphoenolpyruvate: sugar phosphotransferase systems and sugar metabolism in Brevibacterium flavum. Agric Biol Chem 51:8. https://doi.org/10.1080/00021369.1987.10868474
Moon MW, Kim HJ, Oh TK, Shin CS, Lee JS, Kim SJ, Lee JK (2005) Analyses of enzyme II gene mutants for sugar transport and heterologous expression of fructokinase gene in Corynebacterium glutamicum ATCC 13032. Fems Microbiol Lett 244:259–266. https://doi.org/10.1016/j.femsle.2005.01.053
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 12:43–50. https://doi.org/10.1159/000096458
Morinaga T, Matsuse T, Ashida H, Yoshida K (2010) Differential substrate specificity of two inositol transporters of Bacillus subtilis. Biosci Biotechnol Biochem 74:1312–1314. https://doi.org/10.1271/bbb.100125
Porco A, Peekhaus N, Bausch C, Tong S, Isturiz T, Conway T (1997) Molecular genetic characterization of the Escherichia coli gntT gene of GntI, the main system for gluconate metabolism. J Bacteriol 179:1584–1590. https://doi.org/10.1128/jb.179.5.1584-1590.1997
Reizer A, Deutscher J, Saier MH Jr, Reizer J (1991) Analysis of the gluconate (gnt) operon of Bacillus subtilis. Mol Microbiol 5:1081–1089. https://doi.org/10.1111/j.1365-2958.1991.tb01880.x
Seibold GM, Wurst M, Eikmanns BJ (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
Stansen C, Uy D, Delaunay S, Eggeling L, Goergen JL, Wendisch VF (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
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 154:264–274. https://doi.org/10.1099/mic.0.2007/008862-0
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 78:309–318. https://doi.org/10.1007/s00253-007-1313-1
Tanaka Y, Teramoto H, Inui M, Yukawa H (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
Tanaka Y, Teramoto H, Inui M, Yukawa H (2011) Translation efficiency of antiterminator proteins is a determinant for the difference in glucose repression of two beta-glucoside phosphotransferase system gene clusters in Corynebacterium glutamicum R. J Bacteriol 193:349–357. https://doi.org/10.1128/JB.01123-10
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 194:6527–6536. https://doi.org/10.1128/jb.01635-12
Tateno T, Fukuda H, Kondo A (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
Taw MN, Lee HI, Lee SH, Chang WS (2015) Characterization of MocR, a GntR-like transcriptional regulator, in Bradyrhizobium japonicum: its impact on motility, biofilm formation, and soybean nodulation. J Microbiol 53:518–525. https://doi.org/10.1007/s12275-015-5313-z
Teramoto H, Inui M, Yukawa H (2011) Transcriptional regulators of multiple genes involved in carbon metabolism in Corynebacterium glutamicum. J Biotechnol 154:114–125. https://doi.org/10.1016/j.jbiotec.2011.01.016
Wang YY, Xu JZ, Zhang WG (2019) Metabolic engineering of l-leucine production in Escherichia coli and Corynebacterium glutamicum: a review. Crit Rev Biotechnol 39:633–647. https://doi.org/10.1080/07388551.2019.1577214
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 182:3088–3096. https://doi.org/10.1128/jb.182.11.3088-3096.2000
Xu J, Zhang J, Liu D, Zhang W (2016) Increased glucose utilization and cell growth of Corynebacterium glutamicum by modifying the glucose-specific phosphotransferase system (PTS(Glc)) genes. Can J Microbiol 62:983–992. https://doi.org/10.1139/cjm-2016-0027
Xu JZ, Yang HK, Zhang WG (2018) NADPH metabolism: a survey of its theoretical characteristics and manipulation strategies in amino acid biosynthesis. Crit Rev Biotechnol 38:1061–1076. https://doi.org/10.1080/07388551.2018.1437387
Xu JZ, Yu HB, Han M, Liu LM, Zhang WG (2019) Metabolic engineering of glucose uptake systems in Corynebacterium glutamicum for improving the efficiency of l-lysine production. J Ind Microbiol Biotechnol 46:937–949. https://doi.org/10.1007/s10295-019-02170-w
Xu JZ, Ruan HZ, Yu HB, Liu LM, Zhang W (2020) Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of l-lysine production from mixed sugar. Microb Cell Fact 19:39. https://doi.org/10.1186/s12934-020-1294-7
Zhang C, Zhang J, Kang Z, Du G, Chen J (2015) Rational engineering of multiple module pathways for the production of l-phenylalanine in Corynebacterium glutamicum. J Ind Microbiol Biotechnol 42:787–797. https://doi.org/10.1007/s10295-015-1593-x
Zhou Z, Wang C, Xu H, Chen Z, Cai H (2015) Increasing succinic acid production using the PTS-independent glucose transport system in a Corynebacterium glutamicum PTS-defective mutant. J Ind Microbiol Biotechnol 42:1073–1082. https://doi.org/10.1007/s10295-015-1630-9
Acknowledgements
We thank Prof. Weiguo Zhang from School of Biotechnology at Jiangnan University for assistance in manuscript writing. This work was supported by the National Natural Science Foundation of China (Grant number 31601459); the China Postdoctoral Science Foundation (Grant number 2016M590410); and the Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions, the 111 project (Grant number 111-2-06).
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Ruan, H., Yu, H. & Xu, J. The glucose uptake systems in Corynebacterium glutamicum: a review. World J Microbiol Biotechnol 36, 126 (2020). https://doi.org/10.1007/s11274-020-02898-z
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DOI: https://doi.org/10.1007/s11274-020-02898-z