Metabolic Fluxes in Lactic Acid Bacteria—A Review

REFERENCES

• Abdel-Rahmana, M., Tashiro, Y., Sonomoto, K. (2011). Lactic acid production from lignocellulose-derived sugars using lactic acid bacteria: overview and limits. J. Biotechnol. 156:286–301.
   PubMed Web of Science ®Google Scholar
• Adamberg, K., Adamberg, S., Laht, T., Ardö, Y., Paalme, T. (2006). Study of cheese associated lactic acid bacteria under carbohydrate-limited conditions using D-stat cultivation. Food Biotechnol. 20:143–160.
   Web of Science ®Google Scholar
• Agrawal, R. (2005). Probiotics: an emerging food supplement with health benefits. Food Biotechnol. 19:227–246.
   Web of Science ®Google Scholar
• Akyol, I., Serdaroglu, K., Gezginc, Y., Sinan Dayisoylu, K., Sait Ekinci, M., Ozkose, E. (2009). Redirection of pyruvate pathway of lactic acid bacteria to improve cheese quality. Food Biotechnol. 23:200–213.
   Web of Science ®Google Scholar
• Andersen, H., Pedersen, M., Hammer, K., Jensen, P. (2001). Lactate dehydrogenase has no control on lactate production but has a strong negative control on formate production in Lactococcus lactis. Eur. J. Biochem. 268:6379–6389.
   Web of Science ®Google Scholar
• Antoniewicz, M. (2013). 13C metabolic flux analysis: optimal design of isotopic labeling experiments. Curr. Opin. Biotechnol. 24:1116–1121.
   PubMed Web of Science ®Google Scholar
• Antoniewicz, M.R., Kelleher, J.K., Stephanopoulos, G. (2007). Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions. Metab. Eng. 9:68–86.
   PubMed Web of Science ®Google Scholar
• Bai, D., Zhao, X., Li, X., Xu, S. (2004). Strain improvement and metabolic flux analysis in the wild-type and a mutant Lactobacillus lactis strain for L(+)-lactic acid production. Biotechnol. Bioeng. 88:681–689.
   PubMed Web of Science ®Google Scholar
• Bailey, J. (1991). Toward a science of metabolic engineering. Science 252:1668–1675.
   PubMed Web of Science ®Google Scholar
• Bhatt, S., Srivastava, S. (2008). Lactic acid production from cane molasses by Lactobacillus delbrueckii NCIM 2025 in submerged condition: optimization of medium component by Taguchi DOE methodology. Food Biotechnol. 22:115–139.
   Web of Science ®Google Scholar
• Becker, S.A., Feist, A.M., Mo, M.L., Hannum, G., Palsson, B.Ø., Herrgard, M.J. (2007). Quantitative prediction of cellular metabolism with constraint based models: the COBRA toolbox. Nature Prot. 2:727–738.
   PubMed Web of Science ®Google Scholar
• Berezina, O., Zakharova, N., Brandt, A., Yarotsky, S., Schwarz, W., Zverlov, V. (2010). Reconstructing the clostridial n-butanol metabolic pathway in Lactobacillus brevis. Appl. Microbiol. Biotechnol. 87:635–646.
   PubMed Web of Science ®Google Scholar
• Bermúdez-Humarán, L., Aubry, C., Motta, J., Deraison, C., Steidler, L., Vergnolle, N., Chatel, J., Langella, P. (2013). Engineering lactococci and lactobacilli for human health. Curr. Opin. Microbiol. 16:278–283.
   PubMed Web of Science ®Google Scholar
• Beste, D.J., Hooper, T., Stewart, G., Bonde, B., Avignone-Rossa, C., Bushell, M.E., Wheeler, P., Klamt, S., Kierzek, A.M., McFadden, J. (2007). GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism. Genome Biol. 8:R89.
   PubMed Web of Science ®Google Scholar
• Boele, J., Olivier, B.G., Teusink, B. (2012). FAME, the flux analysis and modeling environment. BMC Systems Biology. 6:8.
   Web of Science ®Google Scholar
• Boghigian, B., Seth, G., Kiss, R., Pfeifer, B. (2010). Metabolic flux analysis and pharmaceutical production. Metab. Eng. 12:81–95.
   PubMed Web of Science ®Google Scholar
• Bolotin, A., Quinquis, B., Renault, P., Sorokin, A., Dusko Ehrlich, S., Kulakauskas, S., Lapidus, A., Goltsman, E., Mazur, M., Pusch, G., Fonstein, M., Overbeek, R., Kyprides, N., Purnelle, B., Prozzi, D., Ngui, K., Masuy, D., Hancy, F., Burteau, S., Boutry, M., Delcour, J., Goffeau, A., Hols, P. (2004). Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus. Nat. Biotechnol. 22:1554–1558.
   PubMed Web of Science ®Google Scholar
• Branco dos Santos, F., de Vos, W., Teusink, B. (2013). Towards metagenome-scale models for industrial applications—the case of lactic acid bacteria. Curr. Opin. Biotechnol. 24:200–206.
   PubMed Web of Science ®Google Scholar
• Bron, P., Kleerebezem, M. (2011). Engineering lactic acid bacteria for increased industrial functionality. Bioeng. Bugs 2:2, 80–87.
   PubMedGoogle Scholar
• Burguess, C., Smid, E., van Sinderen, D. (2009). Bacterial vitamin B2, B11 and B12 overproduction: an overview. Int. J. Food Microbiol. 133:1–7.
   PubMed Web of Science ®Google Scholar
• Capozzi, V., Russo, P., Dueñas, M., López, P., Spano, G. (2012). Lactic acid bacteria producing B-group vitamins: a great potential for functional cereals products. Appl. Microbiol. Biotechnol. 96:1383–1394.
   PubMed Web of Science ®Google Scholar
• Castillo, F., Balciunas, E., Salgado, J., Domınguez, J., Converti, A., Pinheiro de Souza, R. (2013). Lactic acid properties, applications and production: a review. Trends in Food Sci. & Tech. 30:70–83.
   Web of Science ®Google Scholar
• Cheng, H., Whang, L., Lin, C., Liu, I., Wu, C. (2013). Metabolic flux network analysis of fermentative hydrogen production using Clostridium tyrobutyricum as an example. Biores. Tech. 141:233–239.
   PubMed Web of Science ®Google Scholar
• Chiewchankaset, P., Srimarut, Y., Klanchui, A., Kurdi, P., Plengvidhya, V., Meechai, A. (2012). Systematic identification of Lactobacillus plantarum auxotrophs for fermented Nham using genome-scale metabolic model. J. Biotechnol. 162:327–335.
   PubMed Web of Science ®Google Scholar
• Curic, M., de Richelieu, M., Henriksen, C. (1999). Glucose/citrate cometabolism in Lactococcus lactis subsp. lactis biovar diacetylactis with impaired α-acetolactate decarboxylase. Metab. Eng. 1:291–298.
   PubMed Web of Science ®Google Scholar
• De Boeck, R., Sarmiento-Rubiano, L., Nadal, I., Monedero, V., Pérez-Martínez, G., Yebra, M. (2010). Sorbitol production from lactose by engineered Lactobacillus casei deficient in sorbitol transport system and mannitol-1-phosphate dehydrogenase. Appl. Microbiol. Biotechnol. 85:1915–1922.
   PubMed Web of Science ®Google Scholar
• de Vos, W., Hugenholtz, J. (2004). Engineering metabolic highways in Lactococci and other lactic acid bacteria. Trends Biotechnol. 22:72–79.
   PubMed Web of Science ®Google Scholar
• de Vos, W. (2011). Systems solutions by lactic acid bacteria: from paradigms to practice. Microbial. Cell Factories 10(Suppl. 1):S2.
   Web of Science ®Google Scholar
• Feng, X., Xu, Y., Chen, Y., Tang, Y. (2012). MicrobesFlux: a web platform for drafting metabolic models from the KEGG database. BMC Syst. Biol. 6:94.
   Web of Science ®Google Scholar
• Flahaut, N., Wiersma, A., van de Bunt, B., Martens, D., Schaap, P., Sijtsma, L., dos Santos, V., de Vos, W. (2013). Genome-scale metabolic model for Lactococcus lactis MG1363 and its application to the analysis of flavor formation. Appl. Microbiol. Biotechnol. 97:8729–8739.
   PubMed Web of Science ®Google Scholar
• Gänzle, M., Follador, R. (2012). Metabolism of oligosaccharides and starch in lactobacilli: a review. Front Microbiol. 3:340.
   Web of Science ®Google Scholar
• Gaspar, P., Carvalho, A., Vinga, S., Santos, H., Neves, A. (2013). From physiology to systems metabolic engineering for the production of biochemicals by lactic acid bacteria. Biotechnol. Adv. 31:764–788.
   PubMed Web of Science ®Google Scholar
• González-Rodríguez, I., Gaspar, P., Sánchez, B., Gueimonde, M., Margolles, A., & Neves, A.R. (2013). Catabolism of glucose and lactose in bifidobacterium animalis subsp. lactis, studied by 13C nuclear magnetic resonance. App. & Environ. Microbiol. 79:7628–7638.
   PubMed Web of Science ®Google Scholar
• Goupry, S., Croguennec, T., Gentil, E., Robins, R. (2000). Metabolic flux in glucose/citrate co-fermentation by lactic acid bacteria as measured by isotopic ratio analysis. FEMS Microbiol. Lett. 182:207–211.
   PubMed Web of Science ®Google Scholar
• Grafahrend-Belau, E., Klukas, C., Junker, B.H., Schreiber, F. (2009). FBA-SimVis: interactive visualization of constraint-based metabolic models. Bioinform. 25:2755–2757.
   PubMed Web of Science ®Google Scholar
• Hati, S., Vij, S., Mandal, S., Malik, R., Kumari, V., Khetra, Y. (2014). α-galactosidase activity and oligosaccharides utilization by Lactobacilly during fermentation of soy milk. J. Food Process. & Preserv. 38:1065–1071.
   Web of Science ®Google Scholar
• Heinrich, R., Rapoport, T. (1974). A linear steady-state treatment of enzyme chains. Eur. J. Biochem. 42:89–95.
   PubMedGoogle Scholar
• Hoefnagel, M., Starrenburg, M., Martens, D., Hugenholtz, J., Kleerebezem, M., Van Swam, I., Bongers, R., Westerhoff, H., Snoep, J. (2002). Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis. Microbiol. 148:1003–1013.
   PubMed Web of Science ®Google Scholar
• Hols, P., Kleerebezem, M., Schanck, A., Ferain, T., Hugenholtz, J., Delcour, J., de Vos, W. (1999). Conversion of Lactococcus lactis from homolactic to homoalanine fermentation through metabolic engineering. Nat. Biotechnol. 17:588–592.
   PubMed Web of Science ®Google Scholar
• Hoppe, A., Hoffmann, S., Gerasch, A., Gille, C., Holzhütter, H. (2011). FASIMU: flexible software for flux balance computation series in large metabolic networks. BMC Bioinform. 12:28.
   Web of Science ®Google Scholar
• Hugenholtz, J. (1993). Citrate metabolism in lactic acid bacteria. FEMS Microbiol. Rev. 12:165–178.
   Web of Science ®Google Scholar
• Hugenholtz, J. (2008). The lactic acid bacterium as a cell factory for food ingredient production. Int. Dairy J. 18:466–475.
   Web of Science ®Google Scholar
• Hugenholtz, J., Sybesma, W., Nierop Groot, M., Wisselink, W., Ladero, V., Burgués, K., van Sinderen, D., Piard, J., Eggink, G., Smid, E., Savoy, G., Sesma, F., Cansen, T., Hols, P., Kleerebezem, M. (2002). Metabolic engineering of lactic acid bacteria for the production of nutraceuticals. Antonie van Leeuwenhoek 82:217–235.
   PubMed Web of Science ®Google Scholar
• Jung, T.S., Yeo, H.C., Reddy, S.G. (2009). WEbcoli: an interactive and asynchronous web application for in silico design and analysis of genome-scale E. coli model. Bioinform. 25:2850–2582.
   Google Scholar
• Junker, B.H., Klukas, C., Schreiber, F. (2006). VANTED: a system for advanced data analysis and visualization in the context of biological networks. BMC Bioinform. 7:109.
   Web of Science ®Google Scholar
• Jyoti, B., Suresh, A., Venkatesh, K. (2004). Effect of preculturing conditions on growth of Lactobacillus rhamnosus on medium containing glucose and citrate. Microbiol. Res. 159:35–42.
   PubMed Web of Science ®Google Scholar
• Kacser, H., Burns, J. (1973). The control of flux. Symp. Soc. Exp. Biol. 27:65–104.
   PubMedGoogle Scholar
• Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., Tanabe, M. (2014). Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 42:199–205.
   PubMed Web of Science ®Google Scholar
• Karp, P.D., Ouzounis, C.A., Moore-Kochlacs, C., Goldovsky, L., Kaipa, P., Ahrén, D., López Bigas, N. (2005). Expansion of the BioCyc collection of pathway/genome databases to 160 genomes. Nucleic Acids Res. 33:6083–6089.
   PubMed Web of Science ®Google Scholar
• Keasling, J. (2010). Manufacturing molecules through metabolic engineering. Science 330:1355–1358.
   PubMed Web of Science ®Google Scholar
• Kim, H., Kim, T., Lee, S.Y. (2008). Metabolic flux analysis and metabolic engineering of microorganisms. Mol. BioSyst. 4:113–120.
   PubMed Web of Science ®Google Scholar
• Kim, S., Seol, E., Oh, Y., Wang, G., Park, S. (2009). Hydrogen production and metabolic flux analysis of metabolically engineered Escherichia coli strains. Int. J. Hydro. Energy 34:7417–7427.
   Web of Science ®Google Scholar
• Klamt, S., Saez-Rodriguez, J., Gilles, E.D. (2007). Structural and functional analysis of cellular networks with CellNetAnalyzer. BMC Syst. Biol. 1:2.
   Web of Science ®Google Scholar
• Kleerebezem, M., Hugenholtz, J. (2003). Metabolic pathway engineering in lactic acid bacteria. Curr. Opin. Biotech. 14:232–237.
   PubMed Web of Science ®Google Scholar
• Kleerebezem, M., Bolees, I., Groot, M., Mierau, I., Sybesma, W., Hugenholtz, J. (2002). Metabolic engineering of Lactococcus lactis: the impact of genomics and metabolic modeling. J. Biotechnol. 98:199–213.
   PubMed Web of Science ®Google Scholar
• Kleerebezem, M., Hols, P., Hugenholtz, J. (2000). Lactic acid bacteria as a cell factory: rerouting of carbon metabolism in Lactococcus lactis by metabolic engineering. Enzyme Microb. Tech. 26:840–848.
   PubMed Web of Science ®Google Scholar
• Ladero, V., Ramos, A., Wiersma, A., Goffin, P., Schanck, A., Kleerebezem, M., Hugenholtz, J., Smid, E., Hols, P. (2007). High-level production of the low-calorie sugar sorbitol by Lactobacillus plantarum through metabolic engineering. Appl. Environ. Microb. 73:1864–1872.
   PubMed Web of Science ®Google Scholar
• Lakshmanan, M., Koh, G., Chung, B., Lee, D. (2012). Software applications for flux balance analysis. Brief. in Bioinform. 15:108–122.
   PubMed Web of Science ®Google Scholar
• Le Blanc, J., Laiño, J., Juarez del Valle, M., Vannini, V., van Sinderen, D., Taranto, M., Font de Valdez, G., Savoy de Giori, G., Sesma, F. (2011). B-group vitamin production by lactic acid bacteria–current knowledge and potential application. J. App. Microbiol. 111:1297–1309.
   PubMed Web of Science ®Google Scholar
• Le Fèvre, F., Smidtas, S., Combe, C., Durot, M., d’Alché-Buc, F., Schachter, V. (2009). CycSim—an online tool for exploring and experimenting with genome-scale metabolic models. Bioinform. 25:1987–1988.
   PubMed Web of Science ®Google Scholar
• Lechardeur, D., Cesselin, B., Fernandez, A., Lamberet, G., Garrigues, C., Pedersen, M., Gaudu, P., Gruss, A. (2010). Using heme as an energy boost for lactic acid bacteria. Curr. Opin. Biotech. 22:1–7.
   PubMed Web of Science ®Google Scholar
• Lee, D.-Y., Yun, H., Park, S., Lee, S.Y. (2003). MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis. Bioinform. 19:2144–2146.
   PubMed Web of Science ®Google Scholar
• Lee, S.Y., Park, J.M., Kim, T.Y. (2011). Application of metabolic flux analysis in metabolic engineering. Meth. Enzymol. 498:67–93.
   PubMed Web of Science ®Google Scholar
• Lee, Y., Salminen, S. (2009). Handbook of Probiotics and Prebiotics, 2nd edn. New York: John Wiley & Sons.
   Google Scholar
• Liao, Y.C., Tsai, M.H., Chen, F.C., Hsiung, C.A. (2012). GEMSiRV: a software platform for GEnome-scale metabolic model simulation, reconstruction and visualization. Bioinform. 13:1752–1758.
   Web of Science ®Google Scholar
• Liu, J., Wang, Q., Zou, H., Liu, Y., Wang, J., Gan, K., Xiang, J. (2013). Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution. Micro. Biotechnol. 6:685–693.
   PubMed Web of Science ®Google Scholar
• Liu, S. (2003). Practical implications of lactate and pyruvate metabolism by lactic acid bacteria in food and beverage fermentations. Int. J. Food Microbiol. 83:115–131.
   PubMed Web of Science ®Google Scholar
• Lopez de Felipe, F., Starrenburg, M., Hugenholtz, J. (1997). The role of NADH-oxidation in acetoin and diacetil production from glucose in Lactococcus lactis. FEMS Microbiol. Lett. 156:15– 19.
   Google Scholar
• Lopez de Felipe, F., Kleerebezem, M., de Vos, W., Hugenholtz, J. (1998). Cofactor engineering: a novel approach to metabolic engineering in Lactococcus lactis by controlled expression of NADH oxidase. J. Bacteriol. 180:3804–3808.
   PubMed Web of Science ®Google Scholar
• Mahadevan, R., Schilling, C. (2003). The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. Metabol. Eng. 5:264–276.
   PubMed Web of Science ®Google Scholar
• Makarova, K., Slesarev, A., Wolf, Y., Sorokin, A., Mirkin, B., Koonin, E., Pavlov, A., Pavlova, N., Karamychev, V., Polouchine, N., Shakhova, V., Grigoriev, I., Lou, Y., Rohksare, D., Lucas, S., Huang, K., Goodstein, D.M., Hawkins, T., Plengvidhya, V., Welker, D., Hughes, J., Goh, Y., Benson, A., Baldwin, K., Lee, J.-H., Dıaz-Muniz, I., Dosti, B., Smeianov, V., Wechter, W., Barabote, R., Lorca, G., Altermann, E., Barrangou, R., Ganesan, B., Xie, Y., Rawsthorne, H., Tamir, D., Parker, C., Breidt, F., Broadbent, J., Hutkins, R., O’Sullivan, D., Steele, J., Unlu, G., Saier, M., Klaenhammer, T., Richardson, P., Kozyavkin, S., Weimer, B., Mills, D. (2006). Comparative genomics of the lactic acid bacteria. PNAS 103:15611–15616.
   PubMed Web of Science ®Google Scholar
• Mao, L., Verwoerd, W. (2014). Computational comparison of mediated current generation capacity of Chlamydomonas reinhardtii in photosynthetic and respiratory growth modes. J. Biosci. & Bioeng. 118:565–574.
   PubMed Web of Science ®Google Scholar
• Mazzoli, R., Bosco, F., Mizrahi, I., Bayer, E., Pessione, E. (2014). Towards lactic acid bacteria-based biorefineries. Biotechnol Adv. 32:1216–1236.
   PubMed Web of Science ®Google Scholar
• Medina de Figueroa, R., Alvarez, F., Pesce de Ruiz Holgado, A., Oliver, G., Sesma, F. (2000). Citrate utilization by homo- and heterofermentative lactobacilli. Microbiol. Res. 154:313–320.
   PubMed Web of Science ®Google Scholar
• Mierau, I., Kleerebezem, M. (2005). 10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis. Appl. Microbiol. Biotechnol. 68:705–717.
   PubMed Web of Science ®Google Scholar
• Millard, P., Sokol, S., Letisse, F., Portais, J. (2014). IsoDesign: a software for optimizing the design of 13C metabolic flux analysis experiments. Biotechnol. Bioeng. 111:202–208.
   PubMed Web of Science ®Google Scholar
• Monedero, V., Pérez-Martínez, G., Yebra, M. (2010). Perspectives of engineering lactic acid bacteria for biotechnological polyol production. Appl. Microbiol. Biotechnol. 86:1003–1015.
   PubMed Web of Science ®Google Scholar
• Mozzi, F., Raya, R., Vignolo, G. (2010). Biotechnology of Lactic Acid Bacteria. Novel Applications. New York: Wiley-Blackwell.
   Google Scholar
• Nam, J., Han, K., Yoon, E., Shin, D., Jin, J., Lee, D., Lee, S., Lee, J. (2004). In silico analysis of lactate producing metabolic network in Lactococcus lactis. Enz. Microb. Tech. 35:654–662.
   Web of Science ®Google Scholar
• Nargund, S., Joffe, M.E., Tran, D., Tugarinov, V., Sriram, G. (2013). Nuclear magnetic resonance methods for metabolic fluxomics. Syst. Metabol. Eng. Humana Press. 335–351.
   Google Scholar
• Neves, A.R., Pool, W.A., Kok, J., Kuipers, O.P., Santos, H. (2005). Overview on sugar metabolism and its control in Lactococcus lactis—the input from in vivo NMR. FEMS Microbiol. Rev. 29:531–554.
   PubMed Web of Science ®Google Scholar
• Neves, A.R., Ramos, A., Nunes, M.C., Kleerebezem, M., Hugenholtz, J., de Vos, W.M., Almeida, J., Santos, H. (1999). In vivo nuclear magnetic resonance studies of glycolytic kinetics in Lactococcus lactis. Biotech. & Bioeng ’. 64:200–212.
   PubMed Web of Science ®Google Scholar
• Nielsen, J., Villadsen, J., Lidén, G. (2002). Bioreaction Engineering Principles. New York, NY: Kluwer Academic/Plenum Publishers .
   Google Scholar
• Novak, L., Loubiere, P. (2000). The metabolic network of Lactococcus lactis: distribution of 14C labeled substrates between catabolic and anabolic pathways. J. Bacteriol. 182:1136–1143.
   PubMed Web of Science ®Google Scholar
• Oddone, G., Mills, D., Block, D. (2009). A dynamic genome-scale flux model of Lactococcus lactis to increase specific recombinant protein expression. Metab. Eng. 11:367–381.
   PubMed Web of Science ®Google Scholar
• Oh, Y., Kim, H., Park, S., Kim, M., Ryu, D. (2008). Metabolic-flux analysis of hydrogen production pathway in Citrobacter amalonaticus Y19. Int. J. Hydr. Energy 33:1471–1482.
   Web of Science ®Google Scholar
• Okano, K., Tanaka, T., Ogino, C., Fukuda, H., Kondo, A. (2010). Biotechnological production of enantiomeric pure lactic acid from renewable resources: recent achievements, perspectives, and limits. Appl. Microbiol. Biotechnol. 85:413–423.
   PubMed Web of Science ®Google Scholar
• Olguín, N., Bordons, A., Reguant, C. (2009). Influence of ethanol and pH on the gene expression of the citrate pathway in Oenococcus oeni. Food Microbiol. 26:197–203.
   PubMed Web of Science ®Google Scholar
• Oliveira, A., Nielsen, J., Förster, J. (2005). Modeling Lactococcus lactis using a genome-scale flux model. BMC Microbiol. 5:39.
   Web of Science ®Google Scholar
• Orman, M., Ierapetritou, M., Androulakis, I., Berthiaume, F. (2011). Metabolic response of perfused livers to various xxygenation conditions. Biotech. & Bioeng. 108:2947–2957.
   PubMed Web of Science ®Google Scholar
• Orth, J., Thiele, I., Palsson, B. (2010). What is flux balance analysis? Nat. Biotech. 28:245–248.
   PubMed Web of Science ®Google Scholar
• Otero, J., Nielsen, J. (2010). Industrial systems biology. Biotechnol. Bioeng. 105:439–460.
   PubMed Web of Science ®Google Scholar
• Parajó, J., Alonso, J., Moldes, A. (1997). Production of lactic acid from lignocellulose in a single stage of hydrolysis and fermentation. Food Biotech. 11:45–58.
   Web of Science ®Google Scholar
• Pastink, M., Teusink, B., Hols, P., Visser, S., de Vos, W., Hugenholtz, J. (2009). Genome-scale model of Streptococcus thermophilus LMG18311 for metabolic comparison of lactic acid bacteria. Appl. Environ. Microbiol. 75:3627–3633.
   PubMed Web of Science ®Google Scholar
• Patel, S., Majumder, A., Goyal, A. (2012). Potentials of exopolysaccharides from lactic acid bacteria. Ind. J. Microbiol. 52:3–12.
   Google Scholar
• Patnaik, R., Louie, S., Gavrilovic, V., Perry, K., Stemmer, W., Ryan, C., Cardayré, S. (2002). Genome shuffling of Lactobacillus for improved acid tolerance. Nat. Biotech. 20:707–712.
   PubMed Web of Science ®Google Scholar
• Patra, F., Tomar, S., Arora, S. (2009). Technological and functional applications of low-calorie sweeteners from lactic acid bacteria. J. Food Sci. 74:16–23.
   PubMed Web of Science ®Google Scholar
• Pedersen, M., Gaudu, P., Lechardeur, D., Petit, M., Gruss, A. (2012). Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology. Ann. Rev. Food Sci. Technol. 3:37–58.
   PubMed Web of Science ®Google Scholar
• Pedersen, M., Iversen, S., Sørensen, K., Johansen, E. (2005). The long and winding road from the research laboratory to industrial applications of lactic acid bacteria. FEMS Microbiol. Rev. 29:611–624.
   PubMed Web of Science ®Google Scholar
• Peterbauer, C., Maischberger, T., Haltrich, D. (2011). Food-grade gene expression in lactic acid bacteria. Biotechnol. J. 9:1147–1161.
   Web of Science ®Google Scholar
• Pfeiffer, T., Sánchez-Valdenebro, I., Nuño, J., Montero, F., Schuster, S. (1999). METATOOL: for studying metabolic networks. Bioinform. 15:251–257.
   PubMed Web of Science ®Google Scholar
• Pfeiler, E., Klaenhammer, T. (2007). The genomics of lactic acid bacteria. Trends in Microbiol. 15:546–553.
   PubMed Web of Science ®Google Scholar
• Platteeuw, C., Hugenholtz, J., Starrenburg, M., van Alen-Boerrigter, I., de Vos, W. (1995). Metabolic engineering of Lactococcus lactis: influence of the overproduction of alpha-acetolactate synthase in strains deficient in lactate dehydrogenase as a function of culture conditions. Appl. Environ. Microbiol. 61:3967–3971.
   PubMed Web of Science ®Google Scholar
• Poolman, M., Venkatesh, K., Pidcock, M., Fell, D. (2004). A method for the determination of flux in elementary modes, and its application to Lactobacillus rhamnosus. Biotechnol. Bioeng. 88:601–612.
   PubMed Web of Science ®Google Scholar
• Putri, S., Nakayama, Y., Matsuda, F., Uchikata, T., Kobayashi, S., Matsubara, A., Fukusaki, E. (2013). Current metabolomics: practical applications. J. Biosci. & Bioeng. 115:579–589.
   PubMed Web of Science ®Google Scholar
• Quek, L.E., Wittmann, C., Nielsen, L., Krömer, J. (2009). OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis. Microbial. Cell Fact. 8:8–25.
   PubMed Web of Science ®Google Scholar
• Rafieenia, R., Chaganti, S. (2014). Flux balance analysis of different carbon source fermentation with hydrogen producing Clostridium butyricum using Cell Net Analyzer. Biores. Tech. (in press).
   Google Scholar
• Rocha, I., Maia, P., Evangelista, P., Vilaça, P., Soraes, S., Pinto, J., Nielsen, J., Patil, K., Ferreira, E., Rocha, M. (2010). OptFlux: an open-source software platform for in silico metabolic engineering. BMC Syst. Biol. 4(4):4.
   Web of Science ®Google Scholar
• Roopashri, A., Varadaraj, M. (2014). Hydrolysis of flatulence causing oligosaccharides by α-d-galactosidase of a probiotic Lactobacillus plantarum MTCC 5422 in selected legume flours and elaboration of probiotic attributes in soy-based fermented product. Eur. Food Res. Technol. 239:99–115.
   Web of Science ®Google Scholar
• Rud, I., Solem, C., Jensen, P., Axelsson, L., Naterstad, K. (2008). Co-factor engineering in lactobacilli: effects of uncoupled ATPase activity on metabolic fluxes in Lactobacillus (L.) plantarum and L. sakei. Metab. Eng. 10:207–215.
   Google Scholar
• Saha, B., Racine, F. (2011). Biotechnological production of mannitol and its applications. Appl. Microbiol. Biotechnol. 89:879–891.
   PubMed Web of Science ®Google Scholar
• Salminen, S., von Wright, A., Ouwehand, A. (2004). Lactic Acid Bacteria. New York: Marcel Dekker.
   Google Scholar
• Santos, F., Wegkamp, A., de Vos, W., Smid, E., Hugenholtz, J. (2008). High-level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM1112. Appl. Environ. Microb. 74:3291–3294.
   PubMed Web of Science ®Google Scholar
• Santos Pontes, D., Santiago Pacheco de Azevedo, M., Chatel, J., Langella, P., Azevedo, V., Miyoshi, A. (2011). Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Prot. Expr. & Purif. 79:165–175.
   PubMed Web of Science ®Google Scholar
• Sauer, U. (2006). Metabolic networks in motion: 13C-based flux analysis. Mol. Syst. Biol. 62:1–10.
   Google Scholar
• Schatschneider, S., Persicke, M., Watt, S., Hublik, G., Pühler, A., Niehaus, K., Vorhölter, F. (2013). Establishment, in silico analysis, and experimental verification of a large-scale metabolic network of the xanthan producing Xanthomonas campestris pv. campestris strain B100. J. Biotech. 167:123–134.
   PubMed Web of Science ®Google Scholar
• Sela, D., Chapman, J., Adeuya, A., Kim, J., Chen, F., Whitehead, T., Lapidus, A., Rokhsar, D., Lebrilla, C., German, J., Price, N., Richardson, P., Mills, D. (2008). The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. PNAS 105:18964–18969.
   PubMed Web of Science ®Google Scholar
• Seol, E., Ainala, S., Sekar, B., Park, S. (2014). Metabolic engineering of Escherichia coli strains for co-production of hydrogen and ethanol from glucose. Int. J. Hydro. Energy 39:19323–19330.
   Web of Science ®Google Scholar
• Shanmugam, S., Chaganti, S., Lalman, J., Heath, D. (2014). Using a statistical approach to model hydrogen production from a steam exploded corn stalk hydrolysate fed to mixed anaerobic cultures in an ASBR. Int. J. Hydro. Energy 39:10003–10015.
   Web of Science ®Google Scholar
• Smid, E., van Enckevort, F., Wegkamp, A., Boekhorst, J., Molenaar, D., Hugenholtz, J., Siezen, R., Teusink, B. (2005). Metabolic models for rational improvement of lactic acid bacteria as cell factories. J. Appl. Microb. 98:1326–1331.
   PubMed Web of Science ®Google Scholar
• Song, S., Vieille, C. (2009). Recent advances in the biological production of mannitol. Appl. Microbiol. Biotechnol. 84:55–62.
   PubMed Web of Science ®Google Scholar
• Sroka, J., Bieniasz-Krzywiec, Ł., Gwóźdź, S., Leniowski, D., Łącki, J., Markowski, M., Kierzek, A. M. (2011). Acorn: a grid computing system for constraint based modeling and visualization of the genome scale metabolic reaction networks via a web interface. BMC Bioinform. 12:196.
   Web of Science ®Google Scholar
• Steidler, L., Hans, W., Schotte, L., Neirynck, S., Obermeier, F., Falk, W., Fiers, W., Remaut, E. (2000). Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289:1352–1355.
   PubMed Web of Science ®Google Scholar
• Stephanopoulos, G. (1999). Metabolic fluxes and metabolic engineering. Metab. Eng. 1:1–11.
   PubMed Web of Science ®Google Scholar
• Stephanopoulos, G., Aristidou, A., Nielsen, J. (1998). Metabolic Engineering. Principles and Methodologies. London: Academic Press.
   Google Scholar
• Stephanopoulos, G., Vallino, J. (1991). Network rigidity and metabolic engineering in metabolite overproduction. Science 252:1675–1681.
   PubMed Web of Science ®Google Scholar
• Sybesma, W., Starrenburg, M., Kleerebezem, M., Mierau, I., de Vos, W., Hugenholtz, J. (2003). Increased production of folate by metabolic engineering of Lactococcus lactis. Appl. Environ. Microb. 69:3069–3076.
   Web of Science ®Google Scholar
• Tarahomjoo, S. (2012). Development of vaccine delivery vehicles based on lactic acid bacteria. Mol. Biotechnol. 51:183–199.
   Google Scholar
• Teusink, B., Bachmann, H., Molenaar, D. (2011). Systems biology of lactic acid bacteria: a critical review. Microbial. Cell Fact. 10(Suppl. 1):S11.
   Web of Science ®Google Scholar
• Teusink, B., Smid, E. (2006). Modelling strategies for the industrial exploitation of lactic acid bacteria. Nat. Rev. Microbiol. 4:46–56.
   PubMed Web of Science ®Google Scholar
• Teusink, B., Wiersma, A., Molenaar, D., Francke, C., de Vos, W., Siezen, R., Smid, E. (2006). Analysis of growth of Lactobacillus plantarum WCFS1 on a complex medium using a Genome-scale metabolic model. J. Biol. Chem. 281:40041–40048.
   PubMed Web of Science ®Google Scholar
• Turhan, I., Bialka, K., Demirci, A., Karhan, M. (2010). Enhanced lactic acid production from carob extract by Lactobacillus casei using invertase pretreatment. Food Biotech. 24:364–374.
   Web of Science ®Google Scholar
• van den Broek, L., Hinz, S., Beldman, G., Vincken, J., Voragen, A. (2008). Bifidobacterium carbohydrases—their role in breakdown and synthesis of (potential) prebiotics. Mol. Nutr. Food Res. 52:146–163.
   PubMed Web of Science ®Google Scholar
• van Hylckama, J., Hugenholtz, J. (2007). Mining natural diversity of lactic acid bacteria for flavour and health benefits. Int. Dairy J. 17:1290–1297.
   Web of Science ®Google Scholar
• Venkatesh, K. (1997). Metabolic flux analysis of lactic acid fermentation: effects of pH and lactate ion concentration. Process. Biochem. 32:651–655.
   Web of Science ®Google Scholar
• Villatoro-Hernández, J., Kuipers, O., Saucedo-Cárdenas, O., Montes, R. (2012). Heterologous protein expression by Lactococcus lactis. In: Recombinant Gene Expression: Reviews and Protocols, 3rd edn. Springer Science and Business Media.
   Google Scholar
• Wardani, A., Egawa, S., Nagahisa, K., Shimizu, H., Shioya, S. (2006). Computational prediction of impact of rerouting the carbon flux in metabolic pathway on cell growth and nisin production by Lactococcus lactis. Biochem. Eng. J. 28:220–230.
   Web of Science ®Google Scholar
• Weitzel, M., Nöh, K., Dalman, T., Niedenführ, S., Stute, B., Wiechert, W. (2013). 13CFLUX2—high-performance software suite for 13C-metabolic flux analysis. Bioinformatics 29:143–145.
   PubMed Web of Science ®Google Scholar
• Welman, A., Maddox, I., Archer, R. (2006). Metabolism associated with raised metabolic flux to sugar nucleotide precursors of exopolysaccharides in Lactobacillus delbrueckii subsp. Bulgaricus. J. Ind. Microbiol. Biotechnol. 33:391–400.
   Web of Science ®Google Scholar
• Widiastuti, H., Lee, D., Karimi, I. (2012). In silico simulation for enhancing production of organic acids in Zymomonas mobilis. Comp. Aided Chem. Eng. 31:900–904.
   Google Scholar
• Wiechert, W. (2001). 13C metabolic flux analysis. Metab. Eng. 3:195–206.
   PubMed Web of Science ®Google Scholar
• Wiechert, W., Mollney, M., Petersen, S., de Graaf, A. (2001). A universal framework for 13C metabolic flux analysis. Metab. Eng. 3:265–283.
   PubMed Web of Science ®Google Scholar
• Wisselink, H., Mars, A., van der Meer, P., Eggink, G., Hugenholtz, J. (2004). Metabolic engineering of mannitol production in Lactococcus lactis: influence of overexpression of mannitol 1-phosphate dehydrogenase in different genetic backgrounds. Appl. Environ. Microbiol. 70:4286–4292.
   PubMed Web of Science ®Google Scholar
• Woolston, B., Edgar, S., Stephanopoulos, G. (2013). Metabolic engineering: past and future. Ann. Rev. Chem. Biomol. Eng. 4:259–288.
   PubMed Web of Science ®Google Scholar
• Xu, N., Liu, J., Ai, L., Liu, L. (2014). Reconstruction and analysis of the genome-scale metabolic model of Lactobacillus casei LC2W. Gene (in press).
   Google Scholar
• Yang, J., Wang, Z., Zhu, N., Wang, B., Chen, T., Zhao, X. (2014). Metabolic engineering of Escherichia coli and in silico comparing of carboxylation pathways for high succinate productivity under aerobic conditions. Microbiol. Res. 169:432–440.
   PubMed Web of Science ®Google Scholar
• Yoo, H., Antoniewicz, M.R., Stephanopoulos, G., Kelleher, J.K. (2008). Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line. J. Biol. Chem. 283:20621–20627.
   PubMed Web of Science ®Google Scholar
• Yue, M., Cao, H., Zhang, J., Li, S., Meng, Y., Chen, W., Huang, L., Du, Y. (2013). Improvement of mannitol production by Lactobacillus brevis mutant 3-A5 based on dual-stage pH control and fed-batch fermentations. World J Microbiol. Biotechnol. 29:1923–1930.
   PubMed Web of Science ®Google Scholar
• Zamboni, N., Fendt, S.M., Rühl, M., Sauer, U. (2013). 13C-based metabolic flux analysis. Nat. Prot. 4:878–892.
   Web of Science ®Google Scholar
• Zhang, H., Cai, Y. (2014). Lactic Acid Bacteria. Fundamentals and Practice. Dordrecht: Springer Science+Business Media.
   Google Scholar
• Zhu, Y., Zhang, Y., Li, Y. (2009). Understanding the industrial application potential of lactic acid bacteria through genomics. Appl. Microbiol. Biotechnol. 83:597–610.
   Google Scholar