Catalytic mechanisms of Fe(II)- and 2-Oxoglutarate-dependent oxygenases

Journal of Biological Chemistry

Volumn 290, Issue 34, 2015, Pages 20702-20711

  Martinez, Salette ^a   Hausinger, Robert P ^a,b  

^a Department of Microbiology and Molecular Genetics Michigan State University ^*  (United States)

^b Michigan State University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYMES;

2-OXOGLUTARATE; CATALYTIC MECHANISMS; DESATURATION; EPIMERIZATION; OXIDATIVE TRANSFORMATIONS; OXYGENASES; RING FORMATION;

CATALYSIS;

2 OXOGLUTARIC ACID; ALPHA-KETOGLUTARIC ACID; CARBOXYLYASE; DIOXYGENASE; IRON; ISOENZYME;

BACTERIUM; BIOCATALYSIS; CHEMICAL STRUCTURE; CYCLIZATION; ENZYMOLOGY; GENE EXPRESSION; GENETICS; HALOGENATION; HUMAN; HYDROXYLATION; METABOLISM; OXIDATION REDUCTION REACTION; STEREOISOMERISM;

BACTERIA; BIOCATALYSIS; CARBOXY-LYASES; CYCLIZATION; DIOXYGENASES; GENE EXPRESSION; HALOGENATION; HUMANS; HYDROXYLATION; IRON; ISOENZYMES; KETOGLUTARIC ACIDS; MODELS, MOLECULAR; OXIDATION-REDUCTION; STEREOISOMERISM;

EID: 84939838764     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R115.648691     Document Type: Short Survey

References (85)

1. Abu-Omar, M. M., Loaiza, A., and Hontzeas, N. (2005) Reaction mechanisms of mononuclear non-heme iron oxygenases. Chem. Rev. 105, 2227-2252
2. Srnec, M., Wong, S. D., and Solomon, E. I. (2014) Excited state potential energy surfaces and their interactions in FeIV =O active sites. Dalton Trans. 43, 17567-17577
3. Pau, M. Y. M., Lipscomb, J. D., and Solomon, E. I. (2007) Substrate activation for O2 reactions by oxidized metal centers in biology. Proc. Natl. Acad. Sci. U.S.A. 104, 18355-18362
4. Decker, A., and Solomon, E. I. (2005) Dioxygen activation by copper, heme and non-heme iron enzymes: comparison of electronic structures and reactivities. Curr. Opin. Chem. Biol. 9, 152-163
5. Costas, M., Mehn, M. P., Jensen, M. P., and Que, L., Jr. (2004) Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. Chem. Rev. 104, 939-986
6. Joosten, V., and van Berkel, W. J. H. (2007) Flavoenzymes. Curr. Opin. Chem. Biol. 11, 195-202
7. Hausinger, R. P. (2004) Fe(II)/α-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. Biol. 39, 21-68
8. Loenarz, C., and Schofield, C. J. (2008) Expanding chemical biology of 2-oxoglutarate oxygenases. Nat. Chem. Biol. 4, 152-156
9. Hausinger, R. P. (2015) Biochemical diversity of 2-oxoglutarate-dependent oxygenases. in 2-Oxoglutarate-Dependent Oxygenases (Schofield, C. J., and Hausinger, R. P., eds), pp. 1-58, The Royal Society of Chemistry, Cambridge, UK
10. Rose, N. R., McDonough, M. A., King, O. N. F., Kawamura, A., and Schofield, C. J. (2011) Inhibition of 2-oxoglutarate dependent oxygenases. Chem. Soc. Rev. 40, 4364-4397
11. Gorres, K. L., and Raines, R. T. (2010) Prolyl 4-hydroxylase. Crit. Rev. Biochem. Mol. Biol. 45, 106-124
12. Wanders, R. J. A., Komen, J., and Ferdinandusse, S. (2011) Phytanic acid metabolism in health and disease. Biochim. Biophys. Acta 1811, 498-507
13. Vaz, F. M., and Wanders, R. J. (2002) Carnitine biosynthesis in mammals. Biochem. J. 361, 417-429
14. Ozer, A., and Bruick, R. K. (2007) Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one? Nat. Chem. Biol. 3, 144-153
15. Taabazuing, C. Y., Hangasky, J. A., and Knapp, M. J. (2014) Oxygen sensing strategies in mammals and bacteria. J. Inorg. Biochem. 133, 63-72
16. Shen, L., Song, C.-X., He, C., and Zhang, Y. (2014) Mechanism and function of oxidative reversal of DNA and RNA methylation. Annu. Rev. Biochem. 83, 585-614
17. Trewick, S. C., Henshaw, T. F., Hausinger, R. P., Lindahl, T., and Sedgwick, B. (2002) Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 419, 174-178
18. Johansson, C., Tumber, A., Che, K., Cain, P., Nowak, R., Gileadi, C., and Oppermann, U. (2014) The roles of Jumonji-type oxygenases in human disease. Epigenomics 6, 89-120
19. Mosammaparast, N., and Shi, Y. (2010) Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu. Rev. Biochem. 79, 155-179
20. Hamed, R. B., Gomez-Castellanos, J. R., Henry, L., Ducho, C., McDonough, M. A., and Schofield, C. J. (2013) The enzymes of β-lactam biosynthesis. Nat. Prod. Rep. 30, 21-107
21. Cheng, A.-X., Han, X.-J., Wu, Y.-F., and Lou, H.-X. (2014) The function and catalysis of 2-oxoglutarate-dependent oxygenases involved in plant flavonoid biosynthesis. Int. J. Mol. Sci. 15, 1080-1095
22. Aik, W. S., Chowdhury, R., Clifton, I. J., Hopkinson, R. J., Leissing, T., McDonough, M. A., Nowak, R., Schofield, C. J., and Walport, L. J. (2015) Introduction to structural studies on 2-oxoglutarate-dependent oxygenases and related enzymes. in 2-Oxoglutarate-Dependent Oxygenases (Schofield, C. J., and Hausinger, R. P., eds), pp. 59-94, The Royal Society of Chemistry, Cambridge, UK
23. Hegg, E. L., and Que, L., Jr. (1997) The 2-His-1-carboxylate facial triad: an emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur. J. Biochem. 250, 625-629
24. Aik, W., McDonough, M. A., Thalhammer, A., Chowdhury, R., and Schofield, C. J. (2012) Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases. Curr. Opin. Struct. Biol. 22, 691-700
25. Clifton, I. J., McDonough, M. A., Ehrismann, D., Kershaw, N. J., Granatino, N., and Schofield, C. J. (2006) Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins. J. Inorg. Biochem. 100, 644-669
26. Eichhorn, E., van der Ploeg, J. R., Kertesz, M. A., and Leisinger, T. (1997) Characterization of α-ketoglutarate-dependent taurine dioxygenase from Escherichia coli. J. Biol. Chem. 272, 23031-23036
27. Proshlyakov, D. A., and Hausinger, R. P. (2011) Transient iron species in the catalytic mechanism of the archetypal α-ketoglutarate-dependent dioxygenase, TauD. in Iron-Containing Enzymes: Versatile Catalysts of Hydroxylation Reactions in Nature (de Visser, S. P., and Kumar, D., eds), pp. 67-87, The Royal Society of Chemistry, Cambridge, UK
28. Vaillancourt, F. H., Yin, J., and Walsh, C. T. (2005) SyrB2 in syringomycin E biosynthesis is a nonheme FeII α-ketoglutarate- and O2-dependent halogenase. Proc. Natl. Acad. Sci. U.S.A. 102, 10111-10116
29. Stapon, A., Li, R., and Townsend, C. A. (2003) Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline. J. Am. Chem. Soc. 125, 8486-8493
30. Topf, M., Sandala, G. M., Smith, D. M., Schofield, C. J., Easton, C. J., and Radom, L. (2004) The unusual bifunctional catalysis of epimerization and desaturation by carbapenem synthase. J. Am. Chem. Soc. 126, 9932-9933
31. Valegård, K., van Scheltinga, A. C. T., Lloyd, M. D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H.-J., Baldwin, J. E., Schofield, C. J., Hajdu, J., and Andersson, I. (1998) Structure of a cephalosporin synthase. Nature 394, 805-809
32. Tarhonskaya, H., Szöllössi, A., Leung, I. K. H., Bush, J. T., Henry, L., Chowdhury, R., Iqbal, A., Claridge, T. D. W., Schofield, C. J., and Flashman, E. (2014) Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases. Biochemistry 53, 2483-2493
33. Li, J., van Belkum, M. J., and Vederas, J. C. (2012) Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna. Bioorg. Med. Chem. 20, 4356-4363
34. Steffan, N., Grundmann, A., Afiyatullov, S., Ruan, H., and Li, S.-M. (2009) FtmOx1, a non-heme Fe(II) and α-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus. Org. Biomol. Chem. 7, 4082-4087
35. Hanauske-Abel, H. M., and Günzler, V. (1982) A stereochemical concept for the catalytic mechanism of prolylhydroxylase: applicability to classification and design of inhibitors. J. Theor. Biol. 94, 421-455
36. Borowski, T., Bassan, A., and Siegbahn, P. E. M. (2004) Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: a hybrid DFT study. Chem.-Eur. J. 10, 1031-1041
37. Bollinger, J. M., Jr., Price, J. C., Hoffart, L. M., Barr, E. W., and Krebs, C. (2005) Mechanism of taurine:α-ketoglutarate dioxygenase (TauD) from Escherichia coli. Eur. J. Inorg. Chem. 2005, 4245-4254
38. Krebs, C., Galonić Fujimori, D., Walsh, C. T., and Bollinger, J. M., Jr. (2007) Non-heme Fe(IV)-oxo intermediates. Acc. Chem. Res. 40, 484-492
39. Grzyska, P. K., Appelman, E. H., Hausinger, R. P., and Proshlyakov, D. A. (2010) Insight into the mechanism of an iron dioxygenase by resolution of steps following the FeIV =O species. Proc. Natl. Acad. Sci. U.S.A. 107, 3982-3987
40. Elkins, J. M., Ryle, M. J., Clifton, I. J., Dunning Hotopp, J. C., Lloyd, J. S., Burzlaff, N. I., Baldwin, J. E., Hausinger, R. P., and Roach, P. L. (2002) X-ray crystal structure of Escherichia coli taurine/α-ketoglutarate dioxygenase complexed to ferrous iron and substrates. Biochemistry 41, 5185-5192
41. Ryle, M. J., Padmakumar, R., and Hausinger, R. P. (1999) Stopped-flow kinetic analysis of Escherichia coli taurine/α-ketoglutarate dioxygenase: interactions with α-ketoglutarate, taurine, and oxygen. Biochemistry 38, 15278-15286
42. Ho, R. Y. N., Mehn, M. P., Hegg, E. L., Liu, A., Ryle, M. J., Hausinger, R. P., and Que, L., Jr. (2001) Resonance Raman studies of the iron(II)-α-keto acid chromophore in model and enzyme complexes. J. Am. Chem. Soc. 123, 5022-5029
43. Neidig, M. L., Brown, C. D., Light, K. M., Fujimori, D. G., Nolan, E. M., Price, J. C., Barr, E. W., Bollinger, J. M., Jr., Krebs, C., Walsh, C. T., and Solomon, E. I. (2007) CD and MCD of CytC3 and taurine dioxygenase: role of the facial triad in α-KG-dependent oxygenases. J. Am. Chem. Soc. 129, 14224-14231
44. Price, J. C., Barr, E. W., Tirupati, B., Bollinger, J. M., Jr., and Krebs, C. (2003) The first direct characterization of a high-valent iron intermediate in the reaction of an α-ketoglutarate-dependent dioxygenase: a high-spin Fe(IV) complex in taurine/α-ketoglutarate dioxygenase (TauD) from Escherichia coli. Biochemistry 42, 7497-7508
45. Hoffart, L. M., Barr, E. W., Guyer, R. B., Bollinger, J. M., Jr., and Krebs, C. (2006) Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase. Proc. Natl. Acad. Sci. U.S.A. 103, 14738-14743
46. Riggs-Gelasco, P. J., Price, J. C., Guyer, R. B., Brehm, J. H., Barr, E. W., Bollinger, J. M., Jr., and Krebs, C. (2004) EXAFS spectroscopic evidence for an Feo=O unit in the Fe(IV) intermediate observed during oxygen activation by taurine:α-ketoglutarate dioxygenase. J. Am. Chem. Soc. 126, 8108-8109
47. Proshlyakov, D. A., Henshaw, T. F., Monterosso, G. R., Ryle, M. J., and Hausinger, R. P. (2004) Direct detection of oxygen intermediates in the non-heme Fe enzyme taurine/α-ketoglutarate dioxygenase. J. Am. Chem. Soc. 126, 1022-1023
48. Price, J. C., Barr, E. W., Glass, T. E., Krebs, C., and Bollinger, J. M., Jr. (2003) Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV) intermediate detected during oxygen activation by taurine:α-ketoglutarate dioxygenase (TauD). J. Am. Chem. Soc. 125, 13008-13009
49. Fang, D., and Cisneros, G. A. (2014) Alternative pathway for the reaction catalyzed by DNA dealkylase AlkB from ab initio QM/MM calculations. J. Chem. Theory Comput. 10, 5136-5148
50. Butler, A., and Sandy, M. (2009) Mechanistic considerations of halogenating enzymes. Nature 460, 848-854
51. Blasiak, L. C., and Drennan, C. L. (2009) Structural perspective on enzymatic halogenation. Acc. Chem. Res. 42, 147-155
52. Vaillancourt, F. H., Yeh, E., Vosburg, D. A., Garneau-Tsodikova, S., and Walsh, C. T. (2006) Nature's inventory of halogenation catalysts: oxidative strategies predominate. Chem. Rev. 106, 3364-3378
53. Hillwig, M. L., and Liu, X. (2014) A new family of iron-dependent halogenases acts on freestanding substrates. Nat. Chem. Biol. 10, 921-923
54. Vaillancourt, F. H., Yeh, E., Vosburg, D. A., O'Connor, S. E., and Walsh, C. T. (2005) Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis. Nature 436, 1191-1194
55. Galonić, D. P., Vaillancourt, F. H., and Walsh, C. T. (2006) Halogenation of unactivated carbon centers in natural product biosynthesis: trichlorination of leucine during barbamide biosynthesis. J. Am. Chem. Soc. 128, 3900-3901
56. Ueki, M., Galonić, D. P., Vaillancourt, F. H., Garneau-Tsodikova, S., Yeh, E., Vosburg, D. A., Schroeder, F. C., Osada, H., and Walsh, C. T. (2006) Enzymatic generation of the antimetabolite γ,γ-dichloroaminobutyrate by NRPS and mononuclear iron halogenase action in a Streptomycete. Chem. Biol. 13, 1183-1191
57. Pratter, S. M., Ivkovic, J., Birner-Gruenberger, R., Breinbauer, R., Zangger, K., and Straganz, G. D. (2014) More than just a halogenase: modification of fatty acyl moieties by a trifunctional metal enzyme. ChemBiochem 15, 567-574
58. Blasiak, L. C., Vaillancourt, F. H., Walsh, C. T., and Drennan, C. L. (2006) Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature 440, 368-371
59. Wong, C., Fujimori, D. G., Walsh, C. T., and Drennan, C. L. (2009) Structural analysis of an open active site conformation of nonheme iron halogenase CytC3. J. Am. Chem. Soc. 131, 4872-4879
60. Wong, S. D., Srnec, M., Matthews, M. L., Liu, L. V., Kwak, Y., Park, K., Bell, C. B., 3rd, Alp, E. E., Zhao, J., Yoda, Y., Kitao, S., Seto, M., Krebs, C., Bollinger, J. M., Jr., and Solomon, E. I. (2013) Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2. Nature 499, 320-323
61. Galonić, D. P., Barr, E. W., Walsh, C. T., Bollinger, J. M., Jr., and Krebs, C. (2007) Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3. Nat. Chem. Biol. 3, 113-116
62. Fujimori, D. G., Barr, E. W., Matthews, M. L., Koch, G. M., Yonce, J. R., Walsh, C. T., Bollinger, J. M., Jr., Krebs, C., and Riggs-Gelasco, P. J. (2007) Spectroscopic evidence for a high-spin Br-Fe(IV)-oxo intermediate in the α-ketoglutarate-dependent halogenase CytC3 from Streptomyces. J. Am. Chem. Soc. 129, 13408-13409
63. Solomon, E. I., Brunold, T. C., Davis, M. I., Kemsley, J. N., Lee, S. K., Lehnert, N., Neese, F., Skulan, A. J., Yang, Y.-S., and Zhou, J. (2000) Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem. Rev. 100, 235-350
64. Matthews, M. L., Krest, C. M., Barr, E. W., Vaillancourt, F. H., Walsh, C. T., Green, M. T., Krebs, C., and Bollinger, J. M. (2009) Substrate-triggered formation and remarkable stability of the C-H bond-cleaving chloroferryl intermediate in the aliphatic halogenase, SyrB2. Biochemistry 48, 4331-4343
65. Pratter, S. M., Light, K. M., Solomon, E. I., and Straganz, G. D. (2014) The role of chloride in the mechanism of O2 activation at the mononuclear nonheme Fe(II) center of the halogenase HctB. J. Am. Chem. Soc. 136, 9385-9395
66. Matthews, M. L., Neumann, C. S., Miles, L. A., Grove, T. L., Booker, S. J., Krebs, C., Walsh, C. T., and Bollinger, J. M., Jr. (2009) Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2. Proc. Natl. Acad. Sci. U.S.A. 106, 17723-17728
67. Kulik, H. J., and Drennan, C. L. (2013) Substrate placement influences reactivity in non-heme Fe(II) halogenases and hydroxylases. J. Biol. Chem. 288, 11233-11241
68. Matthews, M. L., Chang, W.-c., Layne, A. P., Miles, L. A., Krebs, C., and Bollinger Jr., J. M. (2014) Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase. Nat. Chem. Biol. 10, 209-215
69. Zhang, Z., Ren, J., Stammers, D. K., Baldwin, J. E., Harlos, K., and Schofield, C. J. (2000) Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat. Struct. Biol. 7, 127-133
70. Zhou, J., Kelly, W. L., Bachmann, B. O., Gunsior, M., Townsend, C. A., and Solomon, E. I. (2001) Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123, 7388-7398
71. Iwata-Reuyl, D., Basak, A., and Townsend, C. A. (1999) β-Secondary kinetic isotope effects in the clavaminate synthase-catalyzed oxidative cyclization of proclavaminic acid and in related azetidinone model reactions. J. Am. Chem. Soc. 121, 11356-11368
72. Borowski, T., de Marothy, S., Broclawik, E., Schofield, C. J., and Siegbahn, P. E. M. (2007) Mechanism for cyclization reaction by clavaminic acid synthase: insights from modeling studies. Biochemistry 46, 3682-3691
73. Borowski, T., Broclawik, E., Schofield, C. J., and Siegbahn, P. E. M. (2006) Epimerization and desaturation by carbapenem synthase (CarC): a hybrid DFT study. J. Comput. Chem. 27, 740-748
74. Bollinger, J. M., Jr., Chang, W.-c., Matthews, M. L., Martinie, R. J., Boal, A. K., and Krebs, C. (2015) Mechanisms of 2-oxoglutarate-dependent oxygenases: the hydroxylation paradigm and beyond. in 2-Oxoglutarate-Dependent Oxygenases (Schofield, C. J., and Hausinger, R. P., eds), pp. 95-122, The Royal Society of Chemistry, Cambridge, UK
75. Stapon, A., Li, R., and Townsend, C. A. (2003) Synthesis of (3S,5R)-carbapenam-3-carboxylic acid and its role in carbapenem biosynthesis and the stereoinversion problem. J. Am. Chem. Soc. 125, 15746-15747
76. Clifton, I. J., Doan, L. X., Sleeman, M. C., Topf, M., Suzuki, H., Wilmouth, R. C., and Schofield, C. J. (2003) Crystal structure of carbapenem synthase (CarC). J. Biol. Chem. 278, 20843-20850
77. Chang, W.-c., Guo, Y., Wang, C., Butch, S. E., Rosenzweig, A. C., Boal, A. K., Krebs, C., and Bollinger, J. M., Jr. (2014) Mechanism of the C5 stereoinversion reaction in the biosynthesis of carbapenem antibiotics. Science 343, 1140-1144
78. Lloyd, M. D., Lee, H.-J., Harlos, K., Zhang, Z.-H., Baldwin, J. E., Schofield, C. J., Charnock, J. M., Garner, C. D., Hara, T., Terwisscha van Scheltinga, A. C., Valegård, K., Viklund, J. A. C., Hajdu, J., Andersson, I., Danielsson, Å., and Bhikhabhai, R. (1999) Studies on the active site of deacetoxycephalosporin C synthase. J. Mol. Biol. 287, 943-960
79. Hashimoto, T., and Yamada, Y. (1987) Purification and characterization of hyoscyamine 6β-hydroxylase from root cultures of Hyoscyamus niger L. Eur. J. Biochem. 164, 277-285
80. Hashimoto, T., Matsuda, J., and Yamada, Y. (1993) Two-step epoxidation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6β-hydroxylase. FEBS Lett. 329, 35-39
81. Moran, G. R. (2014) 4-Hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase: exemplars of the α-keto acid dependent oxygenases. Arch. Biochem. Biophys. 544, 58-68
82. Roach, P. L., Clifton, I. J., Hensgens, C. M. H., Shibata, N., Schofield, C. J., Hajdu, J., and Baldwin, J. E. (1997) Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation. Nature 387, 827-830
83. Brisson, L., El. Bakkali-Taheri, N., Giorgi, M., Fadel, A., Kaizer, J., Réglier, M., Tron, T., Ajandouz, E. H., and Simaan, A. J. (2012) 1-Aminocyclopropane-1-carboxylic acid oxidase: insight into cofactor binding from experimental and theoretical studies. J. Biol. Inorg. Chem. 17, 939-949
84. Nair, S. K., and van der Donk, W. A. (2011) Structure and mechanism of enzymes involved in biosynthesis and breakdown of the phosphonates fosfomycin, dehydrophos, and phosphinothricin. Arch. Biochem. Biophys. 505, 13-21
85. Chang, W. C., Dey, M., Liu, P., Mansoorabadi, S. O., Moon, S. J., Zhao, Z. B. K., Drennan, C. L., and Liu, H. W. (2013) Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration reaction. Nature 496, 114-118