Engineering specialized metabolic pathways-is there a room for enzyme improvements?

Current Opinion in Biotechnology

Volumn 24, Issue 2, 2013, Pages 310-319

  Bar Even, Arren ^a   Salah Tawfik, Dan ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

BIOSYNTHESIS PATHWAYS; CATALYTIC EFFICIENCIES; CATALYZE REACTION; ENZYME ENGINEERING; PATHWAY ENGINEERINGS; RELATIVE ABUNDANCE; SECONDARY METABOLISM; SPONTANEOUS REACTIONS;

BIOCHEMICAL ENGINEERING; BIOCHEMISTRY; EFFICIENCY; ENGINEERING; ENZYMES; METABOLISM; PHYSIOLOGY;

METABOLIC ENGINEERING;

ADENOSINE TRIPHOSPHATE; BACTERIAL ENZYME; BETALAIN; CYTOCHROME P450; DOPA; FUNGAL ENZYME; GLYCOSYLTRANSFERASE; MONOPHENOL MONOOXYGENASE; PHYTOSTEROL; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TYROSINE 3 MONOOXYGENASE;

BACTERIAL METABOLISM; BIOCHEMISTRY; BIOTECHNOLOGY; CATALYSIS; ENZYME ACTIVITY; ENZYME ENGINEERING; ENZYME SPECIFICITY; FUNGAL METABOLISM; METABOLIC ENGINEERING; NONHUMAN; PLANT METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

BIOCATALYSIS; ENZYMES; METABOLIC ENGINEERING; METABOLIC NETWORKS AND PATHWAYS; PROTEIN ENGINEERING; SUBSTRATE SPECIFICITY;

EID: 84874990225     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2012.10.006     Document Type: Review

References (96)

1. Ro D.K., Paradise E.M., Ouellet M., Fisher K.J., Newman K.L., Ndungu J.M., Ho K.A., Eachus R.A., Ham T.S., Kirby J., et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 2006, 440:940-943.
2. Yun D.J., Hashimoto T., Yamada Y. Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition. Proc Natl Acad Sci USA 1992, 89:11799-11803.
3. Chartrain M., Salmon P.M., Robinson D.K., Buckland B.C. Metabolic engineering and directed evolution for the production of pharmaceuticals. Curr Opin Biotechnol 2000, 11:209-214.
4. Steen E.J., Kang Y., Bokinsky G., Hu Z., Schirmer A., McClure A., Del Cardayre S.B., Keasling J.D. Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 2010, 463:559-562.
5. Atsumi S., Hanai T., Liao J.C. Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 2008, 451:86-89.
6. Dellomonaco C., Clomburg J.M., Miller E.N., Gonzalez R. Engineered reversal of the beta-oxidation cycle for the synthesis of fuels and chemicals. Nature 2011, 476:355-359.
7. Wargacki A.J., Leonard E., Win M.N., Regitsky D.D., Santos C.N., Kim P.B., Cooper S.R., Raisner R.M., Herman A., Sivitz A.B., et al. An engineered microbial platform for direct biofuel production from brown macroalgae. Science 2012, 335:308-313.
8. Lan E.I., Liao J.C. Metabolic engineering of cyanobacteria for 1-butanol production from carbon dioxide. Metab Eng 2011, 13:353-363.
9. Yim H., Haselbeck R., Niu W., Pujol-Baxley C., Burgard A., Boldt J., Khandurina J., Trawick J.D., Osterhout R.E., Stephen R., et al. Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol 2011, 7:445-452.
10. Slater S., Mitsky T.A., Houmiel K.L., Hao M., Reiser S.E., Taylor N.B., Tran M., Valentin H.E., Rodriguez D.J., Stone D.A., et al. Metabolic engineering of Arabidopsis and Brassica for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer production. Nat Biotechnol 1999, 17:1011-1016.
11. Spreitzer R.J., Salvucci M.E. Rubisco: structure, regulatory interactions, and possibilities for a better enzyme. Annu Rev Plant Biol 2002, 53:449-475.
12. Greene D.N., Whitney S.M., Matsumura I. Artificially evolved Synechococcus PCC6301 Rubisco variants exhibit improvements in folding and catalytic efficiency. Biochem J 2007, 404:517-524.
13. Tcherkez G.G., Farquhar G.D., Andrews T.J. Despite slow catalysis and confused substrate specificity, all ribulose bisphosphate carboxylases may be nearly perfectly optimized. Proc Natl Acad Sci USA 2006, 103:7246-7251.
14. Savir Y., Noor E., Milo R., Tlusty T. Cross-species analysis traces adaptation of Rubisco toward optimality in a low-dimensional landscape. Proc Natl Acad Sci USA 2010, 107:3475-3480.
15. Knowles J.R., Alberty W.J. Perfection in enzyme catalysis: the energetics of triosephosphate isomerase. Acc Chem Res 1977, 10:105-111.
16. 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 2011, 50:4402-4410.
17. Bar-Even A., Noor E., Lewis N.E., Milo R. Design and analysis of synthetic carbon fixation pathways. Proc Natl Acad Sci USA 2010, 107:8889-8894.
18. Bar-Even A., Noor E., Milo R. A survey of carbon fixation pathways through a quantitative lens. J Exp Bot 2012, 63:2325-2342.
19. Nam H., Lewis N.E., Lerman J.A., Lee D.H., Chang R.L., Kim D., Palsson B.O. Network context and selection in the evolution to enzyme specificity. Science 2012, 337:1101-1104.
20. D'Ari R., Casadesus J. Underground metabolism. Bioessays 1998, 20:181-186.
21. Khersonsky O., Roodveldt C., Tawfik D.S. Enzyme promiscuity: evolutionary and mechanistic aspects. Curr Opin Chem Biol 2006, 10:498-508.
22. Kim J., Kershner J.P., Novikov Y., Shoemaker R.K., Copley S.D. Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5'-phosphate synthesis. Mol Syst Biol 2010, 6:436.
23. Tawfik D.S. Messy biology and the origins of evolutionary innovations. Nat Chem Biol 2010, 6:692-696.
24. Strack D., Vogt T., Schliemann W. Recent advances in betalain research. Phytochemistry 2003, 62:247-269.
25. Stintzing F.C., Carle R. Betalains - emerging prospects for food scientists. Trends Food Sci Technol 2007, 18:514-525.
26. Moreno D.A., Garcia-Viguera C., Gil J.I., Gil-Izquierdo A. Betalains in the era of global agri-food science, technology and nutritional health. Phytochem Rev 2008, 7:261-280.
27. Hernandez-Martinez A.R., Estevez M., Vargas S., Quintanilla F., Rodriguez R. New dye-sensitized solar cells obtained from extracted bracts of bougainvillea glabra and spectabilis betalain pigments by different purification processes. Int J Mol Sci 2011, 12:5565-5576.
28. Lu P., Vogel C., Wang R., Yao X., Marcotte E.M. Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotechnol 2007, 25:117-124.
29. Weng J.K., Philippe R.N., Noel J.P. The rise of chemodiversity in plants. Science 2012, 336:1667-1670.
30. Tsai C.Y. Sucrose-UDP glucosyltransferase of Zea mays endosperm. Phytochemistry 1974, 13:885-891.
31. Vogt T., Grimm R., Strack D. Cloning and expression of a cDNA encoding betanidin 5-O-glucosyltransferase, a betanidin- and flavonoid-specific enzyme with high homology to inducible glucosyltransferases from the Solanaceae. Plant J 1999, 19:509-519.
32. Hans J., Brandt W., Vogt T. Site-directed mutagenesis and protein 3D-homology modelling suggest a catalytic mechanism for UDP-glucose-dependent betanidin 5-O-glucosyltransferase from Dorotheanthus bellidiformis. Plant J 2004, 39:319-333.
33. Boyer C., Preiss J. Biosynthesis of bacterial glycogen. Purification and properties of the Escherichia coli b alpha-1,4,-glucan: alpha-1,4-glucan 6-glycosyltansferase. Biochemistry 1977, 16:3693-3699.
34. Selinheimoa E., Gasparettia C., Mattinena M.L., Steffensenb C.L., Bucherta J., Kruusa K. Comparison of substrate specificity of tyrosinases from Trichoderma reesei and Agaricus bisporus. Enzyme Microb Technol 2009, 44:1-10.
35. Hatlestad G.J., Sunnadeniya R.M., Akhavan N.A., Gonzalez A., Goldman I.L., McGrath J.M., Lloyd A.M. The beet R locus encodes a new cytochrome P450 required for red betalain production. Nat Genet 2012, 44:816-820.
36. Gandia-Herrero F., Garcia-Carmona F. Characterization of recombinant Beta vulgaris 4,5-DOPA-extradiol-dioxygenase active in the biosynthesis of betalains. Planta 2012, 236:91-100.
37. Weng J.K., Li Y., Mo H., Chapple C. Assembly of an evolutionarily new pathway for alpha-pyrone biosynthesis in Arabidopsis. Science 2012, 337:960-964.
38. Bohlmann J., Meyer-Gauen G., Croteau R. Plant terpenoid synthases: molecular biology and phylogenetic analysis. Proc Natl Acad Sci USA 1998, 95:4126-4133.
39. Phillips M.A., Savage T.J., Croteau R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch Biochem Biophys 1999, 372:197-204.
40. Fischbach M.A., Clardy J. One pathway, many products. Nat Chem Biol 2007, 3:353-355.
41. Selinheimo E., NiEidhin D., Steffensen C., Nielsen J., Lomascolo A., Halaouli S., Record E., O'Beirne D., Buchert J., Kruus K. Comparison of the characteristics of fungal and plant tyrosinases. J Biotechnol 2007, 130:471-480.
42. Ekroos M., Sjogren T. Structural basis for ligand promiscuity in cytochrome P450 3A4. Proc Natl Acad Sci USA 2006, 103:13682-13687.
43. Bloom J.D., Romero P.A., Lu Z., Arnold F.H. Neutral genetic drift can alter promiscuous protein functions, potentially aiding functional evolution. Biol Direct 2007, 2:17.
44. Dietrich J.A., Yoshikuni Y., Fisher K.J., Woolard F.X., Ockey D., McPhee D.J., Renninger N.S., Chang M.C., Baker D., Keasling J.D. A novel semi-biosynthetic route for artemisinin production using engineered substrate-promiscuous P450(BM3). ACS Chem Biol 2009, 4:261-267.
45. Notomista E., Scognamiglio R., Troncone L., Donadio G., Pezzella A., Di Donato A., Izzo V. Tuning the specificity of the recombinant multicomponent toluene o-xylene monooxygenase from Pseudomonas sp. strain OX1 for the biosynthesis of tyrosol from 2-phenylethanol. Appl Environ Microbiol 2011, 77:5428-5437.
46. Thalmann C., Lötzbeyer T. Enzymatic cross-linking of proteins with tyrosinase. Eur Food Res Technol 2002, 214:276-281.
47. Luthra P.M., Singh S. Identification and optimization of tyrosine hydroxylase activity in Mucuna pruriens DC. var. utilis. Planta 2010, 231:1361-1369.
48. Austin M.B., O'Maille P.E., Noel J.P. Evolving biosynthetic tangos negotiate mechanistic landscapes. Nat Chem Biol 2008, 4:217-222.
49. Felnagle E.A., Chaubey A., Noey E.L., Houk K.N., Liao J.C. Engineering synthetic recursive pathways to generate non-natural small molecules. Nat Chem Biol 2012, 8:518-526.
50. Nes W.D. Sterol methyl transferase: enzymology and inhibition. Biochim Biophys Acta 2000, 1529:63-88.
51. Ahmed H., Ettema T.J., Tjaden B., Geerling A.C., van der Oost J., Siebers B. The semi-phosphorylative Entner-Doudoroff pathway in hyperthermophilic archaea: a re-evaluation. Biochem J 2005, 390:529-540.
52. Sauerwald A., Zhu W., Major T.A., Roy H., Palioura S., Jahn D., Whitman W.B., Yates J.R., Ibba M., Soll D. RNA-dependent cysteine biosynthesis in archaea. Science 2005, 307:1969-1972.
53. Sasaki N., Wada K., Koda T., Kasahara K., Adachi T., Ozeki Y. Isolation and characterization of cDNAs encoding an enzyme with glucosyltransferase activity for cyclo-DOPA from four o'clocks and feather cockscombs. Plant Cell Physiol 2005, 46:666-670.
54. Gandia-Herrero F., Escribano J., Garcia-Carmona F. Characterization of the monophenolase activity of tyrosinase on betaxanthins: the tyramine-betaxanthin/dopamine-betaxanthin pair. Planta 2005, 222:307-318.
55. Gandia-Herrero F., Escribano J., Garcia-Carmona F. Betaxanthins as substrates for tyrosinase. An approach to the role of tyrosinase in the biosynthetic pathway of betalains. Plant Physiol 2005, 138:421-432.
56. Boerjan W., Ralph J., Baucher M. Lignin biosynthesis. Annu Rev Plant Biol 2003, 54:519-546.
57. Fujioka S., Yokota T. Biosynthesis and metabolism of brassinosteroids. Annu Rev Plant Biol 2003, 54:137-164.
58. Maresca J.A., Graham J.E., Bryant D.A. The biochemical basis for structural diversity in the carotenoids of chlorophototrophic bacteria. Photosynth Res 2008, 97:121-140.
59. Cafaro V., Notomista E., Capasso P., Di Donato A. Regiospecificity of two multicomponent monooxygenases from Pseudomonas stutzeri OX1: molecular basis for catabolic adaptation of this microorganism to methylated aromatic compounds. Appl Environ Microbiol 2005, 71:4736-4743.
60. Nagata N., Tanaka R., Tanaka A. The major route for chlorophyll synthesis includes [3,8-divinyl]-chlorophyllide a reduction in Arabidopsis thaliana. Plant Cell Physiol 2007, 48:1803-1808.
61. Cunningham F.X., Pogson B., Sun Z., McDonald K.A., DellaPenna D., Gantt E. Functional analysis of the beta and epsilon lycopene cyclase enzymes of Arabidopsis reveals a mechanism for control of cyclic carotenoid formation. Plant Cell 1996, 8:1613-1626.
62. Delauney A.J., Verma P.S. Proline biosynthesis and osmoregulation in plants. Plant J 1993, 4:215-223.
63. Land E.J., Riley P.A. Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathways. Pigment Cell Res 2000, 13:273-277.
64. Terradas F., Wyler H. 2,3- and 4,5-Secodopa, the biosynthetic intermediates generated from l-Dopa by an enzyme system extracted from the fly agaric, Amanita muscaria L., and their spontaneous conversion to muscaflavin and betalamic acid, respectively, and betalains. Helv Chim Acta 1991, 74:124-140.
65. Schliemann W., Kobayashi N., Strack D. The decisive step in betaxanthin biosynthesis is a spontaneous reaction. Plant Physiol 1999, 119:1217-1232.
66. O'Brien P.J., Siraki A.G., Shangari N. Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. Crit Rev Toxicol 2005, 35:609-662.
67. Thompson A., Land E.J., Chedekel M.R., Subbarao K.V., Truscott T.G. A pulse radiolysis investigation of the oxidation of the melanin precursors 3,4-dihydroxyphenylalanine (dopa) and the cysteinyldopas. Biochim Biophys Acta 1985, 843:49-57.
68. Calculated concentration of total protein/E. coli cell in exponential phase on glucose medium on World Wide Web URL: http://bionumbers.hms.harvard.edu//bionumber.aspx%3Fid=104726%26ver=18.
69. Pawelek J.M., Lerner A.B. 5,6-Dihydroxyindole is a melanin precursor showing potent cytotoxicity. Nature 1978, 276:626-628.
70. Gravel E., Poupon E. Biogenesis and biomimetic chemistry: can complex natural products be assembled spontaneously?. Eur J Org Chem 2008, 2008:27-42.
71. Nakajima J., Tanaka Y., Yamazaki M., Saito K. Reaction mechanism from leucoanthocyanidin to anthocyanidin 3-glucoside, a key reaction for coloring in anthocyanin biosynthesis. J Biol Chem 2001, 276:25797-25803.
72. O'Connor S.E., Maresh J.J. Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat Prod Rep 2006, 23:532-547.
73. Stockigt J., Chen Z., Ruppert M. Enzymatic and chemo-enzymatic approaches towards natural and non-natural alkaloids: indoles, isoquinolines, and others. Top Curr Chem 2010, 297:67-103.
74. Goldsmith M., Tawfik D.S. Directed enzyme evolution: beyond the low-hanging fruit. Curr Opin Struct Biol 2012, 22:406-412.
75. Bornscheuer U.T., Huisman G.W., Kazlauskas R.J., Lutz S., Moore J.C., Robins K. Engineering the third wave of biocatalysis. Nature 2012, 485:185-194.
76. Wang M., Si T., Zhao H. Biocatalyst development by directed evolution. Bioresour Technol 2012, 115:117-125.
77. Quin M.B., Schmidt-Dannert C. Engineering of biocatalysts - from evolution to creation. ACS Catal 2011, 1:1017-1021.
78. Khersonsky O., Kiss G., Rothlisberger D., Dym O., Albeck S., Houk K.N., Baker D., Tawfik D.S. Bridging the gaps in design methodologies by evolutionary optimization of the stability and proficiency of designed Kemp eliminase KE59. Proc Natl Acad Sci USA 2012, 109:10358-10363.
79. Khare S.D., Kipnis Y., Greisen P., Takeuchi R., Ashani Y., Goldsmith M., Song Y., Gallaher J.L., Silman I., Leader H., et al. Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis. Nat Chem Biol 2012, 8:294-300.
80. Fasan R., Meharenna Y.T., Snow C.D., Poulos T.L., Arnold F.H. Evolutionary history of a specialized p450 propane monooxygenase. J Mol Biol 2008, 383:1069-1080.
81. Gupta R.D., Goldsmith M., Ashani Y., Simo Y., Mullokandov G., Bar H., Ben-David M., Leader H., Margalit R., Silman I., et al. Directed evolution of hydrolases for prevention of G-type nerve agent intoxication. Nat Chem Biol 2011, 7:120-125.
82. Goldsmith M., Ashani Y., Simo Y., Ben-David M., Leader H., Silman I., Sussman J.L., Tawfik D.S. Evolved stereoselective hydrolases for broad-spectrum G-type nerve agent detoxification. Chem Biol 2012, 19:456-466.
83. Garcia-Ruiz E., Gonzalez-Perez D., Ruiz-Duenas F.J., Martinez A.T., Alcalde M. Directed evolution of a temperature-, peroxide- and alkaline pH-tolerant versatile peroxidase. Biochem J 2011, 441:487-498.
84. Campeotto I., Bolt A.H., Harman T.A., Dennis C., Trinh C.H., Phillips S.E., Nelson A., Pearson A.R., Berry A. Structural insights into substrate specificity in variants of N-acetylneuraminic Acid lyase produced by directed evolution. J Mol Biol 2010, 404:56-69.
85. Runguphan W., Glenn W.S., O'Connor S.E. Redesign of a dioxygenase in morphine biosynthesis. Chem Biol 2012, 19:674-678.
86. Winter J.M., Tang Y. Synthetic biological approaches to natural product biosynthesis. Curr Opin Biotechnol 2011, 23:736-743.
87. Fasan R., Crook N.C., Peters M.W., Meinhold P., Buelter T., Landwehr M., Cirino P.C., Arnold F.H. Improved product-per-glucose yields in P450-dependent propane biotransformations using engineered Escherichia coli. Biotechnol Bioeng 2011, 108:500-510.
88. Khersonsky O., Malitsky S., Rogachev I., Tawfik D.S. Role of chemistry versus substrate binding in recruiting promiscuous enzyme functions. Biochemistry 2011, 50:2683-2690.
89. Hollfelder F., Kirby A.J., Tawfik D.S. Off-the-shelf proteins that rival tailor-made antibodies as catalysts. Nature 1996, 383:60-62.
90. Rothlisberger D., Khersonsky O., Wollacott A.M., Jiang L., DeChancie J., Betker J., Gallaher J.L., Althoff E.A., Zanghellini A., Dym O., et al. Kemp elimination catalysts by computational enzyme design. Nature 2008, 453:190-195.
91. Ngaki M.N., Louie G.V., Philippe R.N., Manning G., Pojer F., Bowman M.E., Li L., Larsen E., Wurtele E.S., Noel J.P. Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis. Nature 2012, 485:530-533.
92. Fairhead M., Thony-Meyer L. Bacterial tyrosinases: old enzymes with new relevance to biotechnology. New Biotechnol 2012, 29:183-191.
93. Bar-Even A., Noor E., Flamholz A., Buescher J.M., Milo R. Hydrophobicity and charge shape cellular metabolite concentrations. PLoS Comput Biol 2011, 7:e1002166.
94. 3H]-tyrosine by charcoal. Life Sci 1986, 39:2185-2189.
95. Connor K.L., Colabroy K.L., Gerratana B. A heme peroxidase with a functional role as an l-tyrosine hydroxylase in the biosynthesis of anthramycin. Biochemistry 2011, 50:8926-8936.
96. Bar-Even A., Flamholz A., Noor E., Milo R. Thermodynamic constraints shape the structure of carbon fixation pathways. Biochim Biophys Acta 2012, 1817:1646-1659.