Channeling in native microbial pathways: Implications and challenges for metabolic engineering

Biotechnology Advances

Volumn 35, Issue 6, 2017, Pages 805-814

  Abernathy, Mary H ^a   He, Lian ^a   Tang, Yinjie J ^a  

^a WASHINGTON UNIVERSITY IN ST LOUIS   (United States)

Author keywords

Compartmentalization; Flux; Glycolysis; Isotopic labeling; Thermodynamics; Tunneling

Indexed keywords

COMPLEX NETWORKS; CYTOLOGY; ELECTRON TUNNELING; ENZYMES; FLUXES; ISOTOPES; METABOLISM; PATHOLOGY; THERMODYNAMICS;

CATABOLITE REPRESSION; COMPARTMENTALIZATION; ENGINEERING APPLICATIONS; GLYCOLYSIS; HETEROGENEOUS DISTRIBUTIONS; ISOTOPIC LABELING; REACTION THERMODYNAMICS; REGULATORY MECHANISM;

METABOLIC ENGINEERING;

BIOTECHNOLOGY; CELLS AND CELL COMPONENTS; COMPARTMENTALIZATION; ENZYME ACTIVITY; EUKARYOTE; FLUX MEASUREMENT; GENETIC ENGINEERING; ISOTOPIC ANALYSIS; MICROBIAL ACTIVITY; MOLECULAR ANALYSIS; NATIVE SPECIES; PROKARYOTE; THERMODYNAMICS; TUNNELING;

EUKARYOTA; PROKARYOTA;

MULTIENZYME COMPLEX;

CHEMISTRY; GENETICS; KINETICS; METABOLIC ENGINEERING; METABOLISM; THERMODYNAMICS; TRENDS;

KINETICS; METABOLIC ENGINEERING; METABOLIC NETWORKS AND PATHWAYS; MULTIENZYME COMPLEXES; THERMODYNAMICS;

EID: 85020930713     PISSN: 07349750     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biotechadv.2017.06.004     Document Type: Review

References (97)

1. Antoniewicz, M.R., Kraynie, D.F., Laffend, L.A., González-Lergier, J., Kelleher, J.K., Stephanopoulos, G., Metabolic flux analysis in a nonstationary system: fed-batch fermentation of a high yielding strain of E. coli producing 1,3-propanediol. Metab. Eng. 9 (2007), 277–292.
2. Atkinson, D.E., Conservation of Solvent Capacity and of Energy, Cellular Energy Metabolism and Its Regulation. 1977, Academic Press, San Diego, 13–30.
3. Avalos, J.L., Fink, G.R., Stephanopoulos, G., Compartmentalization of metabolic pathways in yeast mitochondria improves production of branched chain alcohols. Nat. Biotechnol. 31 (2013), 335–341.
4. Baek, J.-M., Mazumdar, S., Lee, S.-W., Jung, M.-Y., Lim, J.-H., Seo, S.-W., Jung, G.-Y., Oh, M.-K., Butyrate production in engineered Escherichia coli with synthetic scaffolds. Biotechnol. Bioeng. 110 (2013), 2790–2794.
5. Baker, P., Pan, D., Carere, J., Rossi, A., Wang, W., Seah, S.Y.K., Characterization of an aldolase − dehydrogenase complex that exhibits substrate channeling in the polychlorinated biphenyls degradation pathway. Biochemistry (Mosc) 48 (2009), 6551–6558.
6. Bar-Even, A., Noor, E., Savir, Y., Liebermeister, W., Davidi, D., Tawfik, D.S., Milo, R., The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters. Biochemistry (Mosc) 50 (2011), 4402–4410.
7. Bauler, P., Huber, G., Leyh, T., McCammon, J.A., Channeling by proximity: the catalytic advantages of active site colocalization using Brownian dynamics. J. Phys. Chem. Lett. 1 (2010), 1332–1335.
8. Bennett, B.D., Kimball, E.H., Gao, M., Osterhout, R., Van Dien, S.J., Rabinowitz, J.D., Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli. Nat. Chem. Biol. 5 (2009), 593–599.
9. 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast. Genome Biol., 6, 2005, R49.
10. Bogorad, I.W., Lin, T.-S., Liao, J.C., Synthetic non-oxidative glycolysis enables complete carbon conservation. Nature 502 (2013), 693–697.
11. Bulutoglu, B., Garcia, K.E., Wu, F., Minteer, S.D., Banta, S., Direct evidence for metabolon formation and substrate channeling in recombinant TCA cycle enzymes. ACS Chem. Biol. 11 (2016), 2847–2853.
12. Chen, A.H., Silver, P.A., Designing biological compartmentalization. Trends Cell Biol. 22 (2012), 662–670 (Special Issue – Synthetic Cell Biology).
13. Chubukov, V., Uhr, M., Le Chat, L., Kleijn, R.J., Jules, M., Link, H., Aymerich, S., Stelling, J., Sauer, U., Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis. Mol. Syst. Biol., 9, 2013, 709.
14. Conrado, R.J., Wu, G.C., Boock, J.T., Xu, H., Chen, S.Y., Lebar, T., Turnšek, J., Tomšič, N., Avbelj, M., Gaber, R., Koprivnjak, T., Mori, J., Glavnik, V., Vovk, I., Benčina, M., Hodnik, V., Anderluh, G., Dueber, J.E., Jerala, R., DeLisa, M.P., DNA-guided assembly of biosynthetic pathways promotes improved catalytic efficiency. Nucleic Acids Res. 40 (2012), 1879–1889.
15. Debnam, P.M., Shearer, G., Blackwood, L., Kohl, D.H., Evidence for channeling of intermediates in the oxidative pentose phosphate pathway by soybean and pea nodule extracts, yeast extracts, and purified yeast enzymes. Eur. J. Biochem. 246 (1997), 283–290 (FEBS).
16. Delebecque, C.j., Lindner, A.B., Silver, P.A., Aldaye, F.A., Organization of intracellular reactions with rationally designed RNA assemblies. Science 333 (2011), 470–474.
17. Dueber, J.E., Wu, G.C., Malmirchegini, G.R., Moon, T.S., Petzold, C.J., Ullal, A.V., Prather, K.L.J., Keasling, J.D., Synthetic protein scaffolds provide modular control over metabolic flux. Nat. Biotechnol. 27 (2009), 753–759.
18. Dunn, M.F., Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex. Arch. Biochem. Biophys. 519 (2012), 154–166.
19. Ellis, R.J., Macromolecular crowding: obvious but underappreciated. Trends Biochem. Sci. 26 (2001), 597–604.
20. Englaender, J.A., Jones, J.A., Cress, B.F., Kuhlman, T.E., Linhardt, R.J., Koffas, M.A.G., Effect of genomic integration location on heterologous protein expression and metabolic engineering in E. coli. ACS Synth. Biol. 6 (2017), 710–720.
21. Eun, C., Kekenes-Huskey, P.M., Metzger, V.T., McCammon, J.A., A model study of sequential enzyme reactions and electrostatic channeling. J. Chem. Phys., 140, 2014.
22. Fendt, S.-M., Buescher, J.M., Rudroff, F., Picotti, P., Zamboni, N., Sauer, U., Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity. Mol. Syst. Biol., 6, 2010, 356.
23. Fischer, E., Sauer, U., Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism. Nat. Genet. 37 (2005), 636–640.
24. 13C constraints. Anal. Biochem. 325 (2004), 308–316.
25. Flamholz, A., Noor, E., Bar-Even, A., Milo, R., eQuilibrator—the biochemical thermodynamics calculator. Nucleic Acids Res. 40 (2012), D770–D775.
26. Flamholz, A., Noor, E., Bar-Even, A., Liebermeister, W., Milo, R., Glycolytic strategy as a tradeoff between energy yield and protein cost. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 10039–10044.
27. Giegé, P., Heazlewood, J.L., Roessner-Tunali, U., Millar, A.H., Fernie, A.R., Leaver, C.J., Sweetlove, L.J., Enzymes of glycolysis are functionally associated with the mitochondrion in Arabidopsis cells. Plant Cell 15 (2003), 2140–2151.
28. Gonzalez, J.E., Antoniewicz, M.R., Tracing metabolism from lignocellulosic biomass and gaseous substrates to products with stable-isotopes. Curr. Opin. Biotechnol. 43 (2017), 86–95.
29. Gottesman, S., Proteases and their targets in Escherichia coli. Annu. Rev. Genet. 30 (1996), 465–506.
30. Grima, R., Schnell, S., Modelling reaction kinetics inside cells. Essays Biochem. 45 (2008), 41–56.
31. Hackett, S.R., Zanotelli, V.R.T., Xu, W., Goya, J., Park, J.O., Perlman, D.H., Gibney, P.A., Botstein, D., Storey, J.D., Rabinowitz, J.D., Systems-level analysis of mechanisms regulating yeast metabolic flux. Science, 354, 2016, aaf2786.
32. He, L., Xiu, Y., Jones, J.A., Baidoo, E.E.K., Keasling, J.D., Tang, Y.J., Koffas, M.A.G., Deciphering flux adjustments of engineered E. coli cells during fermentation with changing growth conditions. Metab. Eng. 39 (2017), 247–256.
33. Hollinshead, W.D., Rodriguez, S., Martin, H.G., Wang, G., Baidoo, E.E.K., Sale, K.L., Keasling, J.D., Mukhopadhyay, A., Tang, Y.J., Examining Escherichia coli glycolytic pathways, catabolite repression, and metabolite channeling using Δpfk mutants. Biotechnol. Biofuels, 9, 2016, 212.
34. Huang, X., Holden, H.M., Raushel, F.M., Channeling of substrates and intermediates in enzyme-catalyzed reactions. Annu. Rev. Biochem. 70 (2001), 149–180.
35. Huege, J., Goetze, J., Schwarz, D., Bauwe, H., Hagemann, M., Kopka, J., Modulation of the major paths of carbon in photorespiratory mutants of Synechocystis. PLoS ONE, 6, 2011, e16278.
36. Huttanus, H.M., Feng, X., Compartmentalized metabolic engineering for biochemical and biofuel production. Biotechnol. J., 1700052, 2017.
37. Ishikawa, M., Tsuchiya, D., Oyama, T., Tsunaka, Y., Morikawa, K., Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex. EMBO J. 23 (2004), 2745–2754.
38. Iwai, M., Takizawa, K., Tokutsu, R., Okamuro, A., Takahashi, Y., Minagawa, J., Isolation of the elusive supercomplex that drives cyclic electron flow in photosynthesis. Nature 464 (2010), 1210–1213.
39. Jandt, U., You, C., Zhang, Y.H.-P., Zeng, A.-P., Compartmentalization and metabolic channeling for multienzymatic biosynthesis: practical strategies and modeling approaches. Zeng, A.-P., (eds.) Fundamentals and Application of New Bioproduction Systems, 2013, Springer, Berlin Heidelberg, 41–65.
40. Jørgensen, K., Rasmussen, A.V., Morant, M., Nielsen, A.H., Bjarnholt, N., Zagrobelny, M., Bak, S., Møller, B.L., Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr. Opin. Plant Biol. 8 (2005), 280–291.
41. Khersonsky, O., Tawfik, D.S., Enzyme promiscuity: a mechanistic and evolutionary perspective. Annu. Rev. Biochem. 79 (2010), 471–505.
42. Kochanowski, K., Gerosa, L., Brunner, S.F., Christodoulou, D., Nikolaev, Y.V., Sauer, U., Few regulatory metabolites coordinate expression of central metabolic genes in Escherichia coli. Mol. Syst. Biol., 13, 2017, 903.
43. Lapuente-Brun, E., Moreno-Loshuertos, R., Acin-Perez, R., Latorre-Pellicer, A., Colas, C., Balsa, E., Perales-Clemente, E., Quiros, P.M., Calvo, E., Rodriguez-Hernandez, M.A., Navas, P., Cruz, R., Carracedo, A., Lopez-Otin, C., Perez-Martos, A., Fernandez-Silva, P., Fernandez-Vizarra, E., Enriquez, J.A., Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science 340 (2013), 1567–1570.
44. Lee, J.H., Jung, S.-C., Bui, L.M., Kang, K.H., Song, J.-J., Kim, S.C., Improved production of l-threonine in Escherichia coli by use of a DNA scaffold system. Appl. Environ. Microbiol. 79 (2013), 774–782.
45. Liebermeister, W., Klipp, E., Bringing metabolic networks to life: convenience rate law and thermodynamic constraints. Theor. Biol. Med. Model., 3, 2006, 41.
46. Link, H., Kochanowski, K., Sauer, U., Systematic identification of allosteric protein-metabolite interactions that control enzyme activity in vivo. Nat. Biotechnol. 31 (2013), 357–361.
47. Liu, F., Rijkers, D.T.S., Post, H., Heck, A.J.R., Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nat. Methods 12 (2015), 1179–1184.
48. Liu, Z., Zhang, Y., Jia, X., Hu, M., Deng, Z., Xu, Y., Liu, T., In vitro reconstitution and optimization of the entire pathway to convert glucose into fatty acid. ACS Synth. Biol. 6 (2017), 701–709.
49. Mashek, D.G., Li, L.O., Coleman, R.A., Long-chain acyl-CoA synthetases and fatty acid channeling. Futur. Lipidol. 2 (2007), 465–476.
50. Meyer, P., Cecchi, G., Stolovitzky, G., Spatial localization of the first and last enzymes effectively connects active metabolic pathways in bacteria. BMC Syst. Biol., 8, 2014.
51. Mika, J.T., Poolman, B., Macromolecule diffusion and confinement in prokaryotic cells. Curr. Opin. Biotechnol., Anal. Biotech. 22 (2011), 117–126.
52. Mika, J.T., Van Den Bogaart, G., Veenhoff, L., Krasnikov, V., Poolman, B., Molecular sieving properties of the cytoplasm of Escherichia coli and consequences of osmotic stress. Mol. Microbiol. 77 (2010), 200–207.
53. Miles, E.W., Tryptophan synthase: a multienzyme complex with an intramolecular tunnel. Chem. Rec. 1 (2001), 140–151.
54. Minton, A.P., The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem. 276 (2001), 10577–10580.
55. Moon, T.S., Dueber, J.E., Shiue, E., Prather, K.L.J., Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli. Metab. Eng. 12 (2010), 298–305.
56. Mourão, M.A., Hakim, J.B., Schnell, S., Connecting the dots: the effects of macromolecular crowding on cell physiology. Biophys. J. 107 (2014), 2761–2766.
57. 13C metabolic flux analysis of Chinese hamster ovary cells in batch culture using extracellular labeling highlights metabolic reversibility and compartmentation. BMC Syst. Biol., 8, 2014, 50.
58. 13C metabolic flux analysis. J. Biosci. Bioeng. 112 (2011), 616–623.
59. Noor, E., Bar-Even, A., Flamholz, A., Reznik, E., Liebermeister, W., Milo, R., Pathway thermodynamics highlights kinetic obstacles in central metabolism. PLoS Comput. Biol., 10, 2014, e1003483.
60. Noor, E., Flamholz, A., Bar-Even, A., Davidi, D., Milo, R., Liebermeister, W., The protein cost of metabolic fluxes: prediction from enzymatic rate laws and cost minimization. PLoS Comput. Biol., 12, 2016, e1005167.
61. Oda, K., New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic peptidases. J. Biochem. 151 (2012), 13–25.
62. Park, J.O., Rubin, S.A., Xu, Y.-F., Amador-Noguez, D., Fan, J., Shlomi, T., Rabinowitz, J.D., Metabolite concentrations, fluxes and free energies imply efficient enzyme usage. Nat. Chem. Biol. 12 (2016), 482–489.
63. Parry, B.R., Surovtsev, I.V., Cabeen, M.T., O'Hern, C.S., Dufresne, E.R., Jacobs-Wagner, C., The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity. Cell 156 (2014), 183–194.
64. Parsons, J.B., Frank, S., Bhella, D., Liang, M., Prentice, M.B., Mulvihill, D.P., Warren, M.J., Synthesis of empty bacterial microcompartments, directed organelle protein incorporation, and evidence of filament-associated organelle movement. Mol. Cell 38 (2010), 305–315.
65. Perham, R.N., Substrate channelling in the pyruvate dehydrogenase multienzyme complex. Biochem. Soc. Trans., 30, 2002, A7.
66. Piedrafita, G., Keller, M.A., Ralser, M., The impact of non-enzymatic reactions and enzyme promiscuity on cellular metabolism during (oxidative) stress conditions. Biomol. Ther. 5 (2015), 2101–2122.
67. Roughan, P.G., Stromal concentrations of coenzyme A and its esters are insufficient to account for rates of chloroplast fatty acid synthesis: evidence for substrate channelling within the chloroplast fatty acid synthase. Biochem. J. 327 (1997), 267–273.
68. Roze, L.V., Chanda, A., Linz, J.E., Compartmentalization and molecular traffic in secondary metabolism: a new understanding of established cellular processes. Fungal Genet. Biol. 48 (2011), 35–48.
69. Sachdeva, G., Garg, A., Godding, D., Way, J.C., Silver, P.A., In vivo co-localization of enzymes on RNA scaffolds increases metabolic production in a geometrically dependent manner. Nucleic Acids Res., 2014, gku617.
70. Schwab, W., Metabolome diversity: too few genes, too many metabolites?. Phytochemistry 62 (2003), 837–849.
71. 2 in intact Escherichia coli. FEBS J. 272 (2005), 3260–3269.
72. Sheng, J., Stevens, J., Feng, X., Pathway compartmentalization in peroxisome of Saccharomyces cerevisiae to produce versatile medium chain fatty alcohols. Sci Rep, 6, 2016, 26884.
73. Spitzer, J., From water and ions to crowded biomacromolecules: in vivo structuring of a prokaryotic cell. Microbiol Mol Biol Rev 75 (2011), 491–506.
74. Srere, P.A., Mattiasson, B., Mosbach, K., An immobilized three-enzyme system: a model for microenvironmental compartmentation in mitochondria. Proc. Natl. Acad. Sci. U. S. A. 70 (1973), 2534–2538.
75. Sumegi, B., Sherry, A.D., Malloy, C.R., Channeling of TCA cycle intermediates in cultured Saccharomyces cerevisiae. Biochemistry (Mosc) 29 (1990), 9106–9110.
76. Sumegi, B., Sherry, A.D., Malloy, C.R., Srere, P.A., Evidence for orientation-conserved transfer in the TCA cycle in Saccharomyces cerevisiae: carbon-13 NMR studies. Biochemistry (Mosc) 32 (1993), 12725–12729.
77. Tan, D., Li, Q., Zhang, M.-J., Liu, C., Ma, C., Zhang, P., Ding, Y.-H., Fan, S.-B., Tao, L., Yang, B., Li, X., Ma, S., Liu, J., Feng, B., Liu, X., Wang, H.-W., He, S.-M., Gao, N., Ye, K., Dong, M.-Q., Lei, X., Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states. elife, 5, 2016.
78. Tang, Y.J., Martin, H.G., Dehal, P.S., Deutschbauer, A., Llora, X., Meadows, A., Arkin, A., Keasling, J.D., Metabolic flux analysis of Shewanella spp. reveals evolutionary robustness in central carbon metabolism. Biotechnol. Bioeng. 102 (2009), 1161–1169.
79. 13C isotopic fingerprints. J. R. Soc. Interface R. Soc. 9 (2012), 2767–2780.
80. Vélot, C., Srere, P.A., Reversible transdominant inhibition of a metabolic pathway. In vivo evidence of interaction between two sequential tricarboxylic acid cycle enzymes in yeast. J. Biol. Chem. 275 (2000), 12926–12933.
81. Verkman, A.S., Solute and macromolecule diffusion in cellular aqueous compartments. Trends Biochem. Sci. 27 (2002), 27–33.
82. Voges, R., Corsten, S., Wiechert, W., Noack, S., Absolute quantification of Corynebacterium glutamicum glycolytic and anaplerotic enzymes by QconCAT. J. Proteome 113 (2015), 366–377.
83. Wang, Y., Yu, O., Synthetic scaffolds increased resveratrol biosynthesis in engineered yeast cells. J. Biotechnol. 157 (2012), 258–260.
84. Weeks, A., Lund, L., Raushel, F., Tunneling of intermediates in enzyme-catalyzed reactions. Curr. Opin. Chem. Biol. 10 (2006), 465–472.
85. Wheeldon, I., Minteer, S.D., Banta, S., Barton, S.C., Atanassov, P., Sigman, M., Substrate channelling as an approach to cascade reactions. Nat. Chem. 8 (2016), 299–309.
86. 13C metabolic flux analysis. Metab. Eng. 3 (2001), 265–283.
87. Williams, T.C.R., Sweetlove, L.J., Ratcliffe, R.G., Capturing metabolite channeling in metabolic flux phenotypes. Plant Physiol. 157 (2011), 981–984.
88. 13C-labeling. Metab. Eng. 3 (2001), 151–162.
89. Worsdorfer, B., Woycechowsky, K.J., Hilvert, D., Directed evolution of a protein container. Science 331 (2011), 589–592.
90. Wortel, M.T., Peters, H., Hulshof, J., Teusink, B., Bruggeman, F.J., Metabolic states with maximal specific rate carry flux through an elementary flux mode. FEBS J. 281 (2014), 1547–1555.
91. Wu, F., Minteer, S., Krebs cycle Metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry. Angew. Chem. Int. Ed. 54 (2015), 1851–1854.
92. Wu, N., Tsuji, S.Y., Cane, D.E., Khosla, C., Assessing the balance between protein − protein interactions and enzyme − substrate interactions in the channeling of intermediates between Polyketide synthase modules. J. Am. Chem. Soc. 123 (2001), 6465–6474.
93. Wu, S.G., Wang, Y., Jiang, W., Oyetunde, T., Yao, R., Zhang, X., Shimizu, K., Tang, Y.J., Bao, F.S., Rapid prediction of bacterial heterotrophic Fluxomics using machine learning and constraint programming. PLoS Comput. Biol., 12, 2016, e1004838.
94. Yan, Y., Li, Z., Koffas, M.A.G., High-yield anthocyanin biosynthesis in engineered Escherichia coli. Biotechnol. Bioeng. 100 (2008), 126–140.
95. 13C flux analysis. Metab. Eng. 13 (2011), 656–665.
96. Zhang, Y.-H.P., Substrate channeling and enzyme complexes for biotechnological applications. Biotechnol. Adv. 29 (2011), 715–725.
97. Zhao, S., Jones, J.A., Lachance, D.M., Bhan, N., Khalidi, O., Venkataraman, S., Wang, Z., Koffas, M.A.G., Improvement of catechin production in Escherichia coli through combinatorial metabolic engineering. Metab. Eng. 28 (2015), 43–53.