Abstract
The assembly of cooperating enzymes into multicatalytic complexes, also known as “metabolons,” has become a well-accepted concept in cellular metabolism, at least in principle. There are still relatively few examples where the existence of such systems is supported by solid experimental evidence and even fewer where there is evidence for “channeling” of metabolites through the complex. However, proteomic approaches are providing new evidence for the pervasiveness of this type of organization, while structural biology is offering insights into how these systems are constructed and regulated. New and improved technologies for analyzing protein interactions and assemblies, both in vitro and in intact cells, are opening the doors to explo-ring the intracellular organization of a growing number of metabolic complexes in plants and other organisms. There is also an increasing appre-ciation of the surprising scale of many protein interaction networks, the multiple functions of individual proteins, and the importance (and challenges) of compartmentalization. As a result, the concept of enzyme complexes is gaining wider acceptance and becoming an increasingly important consideration in efforts to engineer metabolism.
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References
Jorgensen, K.et al (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr. Opin. Plant Biol.8, 280–291
Marsh, B.J.et al (2001) Organellar relationships in the Golgi region of the pancreatic beta cell line, HIT-T15, visualized by high resolution electron tomography. Proc. Natl. Acad. Sci. USA.98, 2399–2406
Uetz, P.et al (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae<. Nature403, 623–627
Giot, L.et al (2003) A protein interaction map of Drosophila melanogaster<. Science302, 1727–1736
Rual, J.F.et al (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature437, 1173–1178
Li, S.et al (2004) A map of the interactome network of the metazoan C. elegans. Science303, 540–543
Han, J.D.et al (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature430, 88–93
Tarassov, K.et al (2008) An in vivo map of the yeast protein interactome. Science320, 1465–1470
Robinson, C.V.et al (2007) The molecular sociology of the cell. Nature450, 973–982
Srere, P.A. (2000) Macromolecular interactions: tracing the roots. Trends Biochem. Sci.25, 150–153
Islam, M.M.et al (2007) A novel branched-chain amino acid metabolon – protein-protein interactions in a supramolecular complex. J. Biol. Chem.282, 11893–11903
Ishikawa, M.et al (2004) Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex. EMBO J.23, 2745–2754
Jenni, S.et al (2006) Architecture of a fungal fatty acid synthase at 5 angstrom resolution. Science311, 1263–1267
Maier, T.et al (2006) Architecture of mammalian fatty acid synthase at 4.5 angstrom resolution. Science311, 1258–1262
Fries, M.et al (2007) Distinct modes of recognition of the lipoyl domain as substrate by the E1 and E3 components of the pyruvate dehydrogenase multienzyme complex. J. Mol. Biol.366, 132–139
Giles, N.H. (1978) The organization, function, and evolution of gene clusters in eucaryotes. Am. Naturalist112, 641–657
Singh, S.A. and Christendat, D. (2007) The DHQ-dehydroshikimate-SDH-shikimate-NADP(H) complex: insights into metabolite transfer in the shikimate pathway. Cryst. Growth Des.7, 2153–2160
Luo, B.et al (2007) Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography-mass spectro-metry. J. Chromatogr. A1147, 153–164
Ishii, N.et al (2007) Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science316, 593–597
Saigne-Soulard, C.et al (2006) C-13 NMR analysis of polyphenol biosynthesis in grape cells: Impact of various inducing factors. Anal. Chim. Acta563, 137–144
Pereira, M.P. and Brown, E.D. (2004) Bifunctional catalysis by CDP-ribitol synthase: Convergent recruitment of reductase and cytidylyltransferase activities in Haemophilus influenzae< and Staphylococcus aureus<. Biochemistry (Mosc).43, 11802–11812
Garcon, A.et al (2006) Crystal structure of the bifunctional dihydroneopterin aldolase/6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Streptococcus pneumoniae<. J. Mol. Biol.360, 644–653
Taglieber, A. et al (2007) Alternate-site enzyme promiscuity. Angew. Chem. Int. Ed.46, 8597–8600
Peisajovich, S.G. and Tawfik, D.S. (2007) Protein engineers turned evolutionists. Nature Methods4, 991–994
Chiron, H.et al (2000) Molecular cloning and functional expression of a stress-induced multifunctional O-methyltransferase with pinosylvin methyltransferase activity from Scots pine (Pinus sylvestris< L.). Plant Mol. Biol.44, 733–745
Frick, S. and Kutchan, T.M. (1999) Molecular cloning and functional expression of O<-methyl-transferases common to isoquinoline alkaloid and phenylpropanoid biosynthesis. Plant J.17, 329–339
Gauthier, A.et al (1998) Characterization of two cDNA clones which encode O<-methyltransferases for the methylation of both flavonoid and phenylpropanoid compounds.Arch. Biochem. Biophys.351, 243–249
He, X.-Z. and Dixon, R.A. (2000) Genetic mani-pulation of isoflavone 7-O-methyltransferase enhances biosynthesis of 4’-O-methylated isoflavonoid phytoalexins and disease resistance in alfalfa. Plant Cell12, 1689–1702
Liu, C.-J. and Dixon, R.A. (2001) Elicitor-induced association of isoflavone O-methyltransferase with endomembranes prevents the formation and 7-O-methylation of daizein during isoflavoniod phytoalexin biosynthesis. Plant Cell13, 2643–2658
Deavours, B.E. et al (2006) Functional analysis of members of the isoflavone and isoflavanone O-methyltransferase enzyme families from the model legume Medicago truncatula. Plant Mol. Biol.62, 715–733
Liu, C.J. et al (2006) Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell18, 3656–3669
Zubieta, C. et al (2001) Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases. Nat. Struct. Biol.8, 271–279
Jenrich, R.et al (2007) Evolution of heteromeric nitrilase complexes in Poaceae with new functions in nitrile metabolism. Proc. Natl. Acad. Sci. USA104, 18848–18853
Kriechbaumer, V.et al (2007) Maize nitrilases have a dual role in auxin homeostasis and β-cyanoalanine hydrolysis. J. Exp. Bot.58, 4225–4233
Kim, S.Y.et al (2005) Novel type of enzyme multimerization enhances substrate affinity of oat β-glucosidase. J. Struct. Biol.150, 1–10
Owens, D.K.et al (2008) Functional analysis of a predicted flavonol synthase gene family in Arabidopsis. Plant Physiol.147, 1046–1061
Kim, S.J.et al (2004) Functional reclassification of the putative cinnamyl alcohol dehydrogenase multigene family in Arabidopsis. Proc. Natl. Acad. Sci. USA101, 1455–1460
Yamagami, T. et al (2003) Biochemical diversity among the 1-amino-cyclopropane-1-carboxylate synthase isozymes encoded by the Arabidopsis gene familyJ. Biol. Chem.278, 49102–49112
Dhugga, K.S. (2007) Maize biomass yield and composition for biofuels. Crop Sci.47, 2211–2227
Somerville, C. (2006) Cellulose synthesis in higher plants. Annu. Rev. Cell Dev. Biol.22, 53–78
Saxena, I.M. and Brown, R.M. (2005) Cellulose biosynthesis: current views and evolving concepts. Ann. Bot.96, 9–21
Mueller, S.C. and Brown, R.M. (1980) Evidence for an intramembrane component associated with a cellulose microfibril-synthesizing complex in higher plants. J. Cell Biol.84, 315–326
Taylor, N.G.et al (2003) Interactions among three distinct CesA proteins essential for cellulose synthesis. Proc. Natl. Acad. Sci. USA100, 1450–1455
Persson, S. et al (2007) Genetic evidence for three unique components in primary cell-wall cellulose synthase complexes in Arabidopsis<. Proc. Natl. Acad. Sci. USA104, 15566–15571
Desprez, T. et al (2007) Organization of cellulose synthase complexes involved in primary cell wall synthesis in Arabidopsis thaliana<. Proc. Natl. Acad. Sci. USA104, 15572–15577
Paradez, A.et al (2006) Microtubule cortical array organization and plant cell morphogenesis. Curr. Opin. Plant Biol.9, 571–578
DeBolt, S.et al (2007) Morlin, an inhibitor of cortical microtubule dynamics and cellulose synthase movement. Proc. Natl. Acad. Sci. USA104, 5854–5859
Chuong, S.D.X.et al (2004) Large-scale identification of tubulin-binding proteins provides insight on subcellular trafficking, metabolic channeling, and signaling in plant cells. Mol. Cell. Proteomics3, 970–983
Hrazdina, G. and Wagner, G.J. (1985) Metabolic pathways as enzyme complexes: evidence for the synthesis of phenylpropanoids and flavonoids on membrane associated enzyme complexes. Arch. Biochem. Biophys.237, 88–100
Hughes, T.R.et al (2000) Functional discovery via a compendium of expression profiles. Cell102, 109–126
Mo, C. and Bard, M. (2005) Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex. J. Lipid Res.46, 1991–1998
Mo, C. and Bard, M. (2005) A systematic study of yeast sterol biosynthetic protein-protein interactions using the split-ubiquitin system. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids1737, 152–160
Ottolenghi, C.et al (2000) The genomic structure of C140rf1 is conserved across eukarya. Mamm. Genome11, 786–788
Burbulis, I.E. and Winkel-Shirley, B. (1999) Interactions among enzymes of the Arabidopsis< flavonoid biosynthetic pathway. Proc. Natl. Acad. Sci. USA96, 12929–12934
Owens, D.K. et al. (2008) Biochemical and genetic characterization of Arabidopsis flavanone 3β-hydroxylase. Plant Physiol. Biochem. 46, 833–843
Kredich, N. et al (1969) Purification and characterization of cysteine synthetase, a bifunctional protein complex, from Salmonella typhimurium<. J. Biol. Chem.244, 2428–2439
Wirtz, M. and Hell, R. (2006) Functional analysis of the cysteine synthase protein complex from plants: Structural, biochemical and regulatory properties. J. Plant Physiol.163, 273–286
Bonner, E.R.et al (2005) Molecular basis of cysteine biosynthesis in plants – structural and functional analysis of O-acetylserine sulfhydrylase from Arabidopsis thaliana<. J. Biol. Chem.280, 38803–38813
Wirtz, M. and Hell, R. (2007) Dominant-negative modification reveals the regulatory function of the multimeric cysteine synthase protein complex in transgenic tobacco. Plant Cell19, 625–639
Francois, J.A. et al (2006) Structural basis for interaction of O-acetylserine sulfhydrylase and serine acetyltransferase in the Arabidopsis< cyst-eine synthase complex. Plant Cell18, 3647–3655
Kumaran, S. and Jez, J.M. (2007) Ther-modynamics of the interaction between O-acetylserine sulfhydrylase and the C-terminus of serine acetyltransferase. Biochemistry (Mosc).46, 5586–5594
Petoukhov, M.V. and Svergun, D.I. (2007) Analysis of X-ray and neutron scattering from biomacromolecular solutions. Curr. Opin. Struct. Biol.17, 562–571
Anderson, L.E. and Carol, A.A. (2005) Enzyme co-localization in the pea leaf cytosol: 3-P-glycerate kinase, glyceraldehyde-3-P dehydrogenase, triose-P isomerase and aldolase. Plant Sci.169, 620–628
Graham, J.W.A.et al (2007) Glycolytic enzymes associate dynamically with mitochondria in response to respiratory demand and support substrate channeling. Plant Cell19, 3723–3738
Dudkina, N.V. et al (2006) Respiratory chain supercomplexes in the plant mitochondrial membrane. Trends Plant Sci.11, 232–240
Winkel, B. (2004) Metabolic channeling in plants. Annu. Rev. Plant Biol.55, 85–107
Facchini, P.J. and St-Pierre, B. (2005) Synthesis and trafficking of alkaloid biosynthetic enzymes. Curr. Opin. Plant Biol.8, 657–666
Gómez-Galera, S.et al (2007) The genetic manipulation of medicinal and aromatic plants. Plant Cell Rep.26, 1689–1715
Morant, A.V. et al (2007) Lessons learned from metabolic engineering of cyanogenic glucosides. Metabolomics3, 383–398
Shimamura, M.et al (2007) 2-hydroxyisoflavanone dehydratase is a critical determinant of isoflavone productivity in hairy root cultures of Lotus japo-nicus. Plant Cell Physiol.48, 1652–1657
Aharoni, A. et al (2005) Volatile science? Metabolic engineering of terpenoids in plants. Trends Plant Sci.10, 594–602
Yan, Y.J.et al (2005) Metabolic engineering of anthocyanin biosynthesis in Escherichia coli<. Appl. Environ. Microbiol.71, 3617–3623
Zalokar, M. (1960) Cytochemistry of centrifuged hyphae of Neurospora<. Exp. Cell Res.19, 114–132
Zalokar, M. (1969) Intracellular centrifugal separation of organelles in Phycomyces<. J. Cell Biol.41, 494–509
Kempner, E.S. and Miller, J.H. (1968) The molecular biology of Euglena gracilis. Exp. Cell Res.51, 141–149
Goehler, H.et al (2005) A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington’s disease (vol 15, pp. 853, 2004). Mol. Cell19, 287–287
Morsy, M.et al (2008) Charting plant interactomes: possibilities and challenges. Trends Plant Sci.13, 183–191
Lalonde, S. et al (2008) Molecular and cellular approaches for the detection of protein-protein interactions: latest techniques and current limitations. Plant J.53, 610–635
Best, C.et al (2007) Localization of protein complexes by pattern recognition. Cell. Electron Microsc.79, 615–638
Adjobo-Hermans, M.J.W.et al (2006) Plant G protein heterotrimers require dual lipidation motifs of G alpha and G gamma and do not dissociate upon activation. J. Cell Sci.119, 5087–5097
Serdyuk, I.N. (2007) Structured proteins and proteins with intrinsic disorder. Mol. Biol.41, 262–277
Dyer, J.M. and Mullen, R.T. (2008) Engineering plant oils as high-value industrial feedstocks for biorefining: the need for underpinning cell biology research. Physiol. Plant.132, 11–22
Giegé, P. et al (2003) Enzymes of glycolysis are functionally associated with the mitochondrion in Arabidopsis cells. Plant Cell15, 2140–2151
Brandina, I.et al (2006) Enolase takes part in a macromolecular complex associated to mitochondria in yeast. Biochim. Biophys. Acta1757, 1217–1228
Jeffery, C.J. (2005) Mass spectrometry and the search for moonlighting proteins. Mass Spectrom. Rev.24, 772–782
Moore, B.D. (2004) Bifunctional and moonlighting enzymes: lighting the way to regulatory control. Trends Plant Sci.9, 221–228
Srere, P.A. (1997) An exception that proves the rule. Trends Biochem. Sci.22, 11–11
Anderson, L.E. et al (2005) Both chloroplastic and cytosolic phosphofructoaldolase isozymes are present in the pea leaf nucleus. Protoplasma225, 235–242
Anderson, L.E.et al (2004) Both chloroplastic and cytosolic phosphoglycerate kinase isozymes are present in the pea leaf nucleus. Protoplasma223, 103–110
Anderson, L.E.et al (2004) Cytosolic glyceraldehyde-3-P dehydrogenase and the B subunit of the chloroplast enzyme are present in the pea leaf nucleus. Protoplasma223, 33–43
Saslowsky, D.et al (2005) Nuclear localization of flavonoid metabolism in Arabidopsis thaliana<. J. Biol. Chem.280, 23735–23740
Shimojima, M.et al (2005) Ferredoxin-dependent glutamate synthase moonlights in plant sulfolipid biosynthesis by forming a complex with SQD1. Arch. Biochem. Biophys.436, 206–214
Matarasso, N. et al (2005) A novel plant cysteine protease has a dual function as a regulator of 1-aminocyclopropane-1-carboxylic acid synthase gene expression. Plant Cell17, 1205–1216
Pollmann, S.et al (2006) Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana<. Planta224, 1241–1253
Lunn, J.E. (2007) Compartmentation in plant metabolism. J. Exp. Bot.58, 35–47
Jeong, H. et al (2001) Lethality and centrality in protein networks. Nature411, 41–42
Vélot, C. et al (1997) Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon. Biochemistry (Mosc).36, 14271–14276
Acknowledgments
The author acknowledges the insights of Joe Chappel (on the erg28p system), Danny Kohl (on the implications of recent metabolic profiling experiments in E. coli), and Joe Noel (on the issue of enzyme promiscuity supporting the existence of enzyme complexes), as well as the very helpful comments of three anonymous reviewers. She is grateful to the National Science Foundation for supporting the work in her laboratory on the flavonoid enzyme complex (currently grant number MCB 0445878). This article is dedicated to the memory of H. Olin Spivey, Professor Emeritus of Biochemistry and Molecular Biology at Oklahoma State University, who died on December 5, 2007. A pioneer in the field of metabolic organization, he will be remembered by many as a valued colleague who encouraged newcomers to join the network.
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Winkel, B.S. (2009). Metabolite Channeling and Multi-enzyme Complexes. In: Osbourn, A., Lanzotti, V. (eds) Plant-derived Natural Products. Springer, New York, NY. https://doi.org/10.1007/978-0-387-85498-4_9
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