Skip to main content
SpringerLink
Log in

Hydrocarbon Oxygenation by Heme-Thiolate Enzymes

  • Chapter
  • First Online:
A Novel Heme-Thiolate Peroxygenase AaeAPO and Its Implications for C-H Activation Chemistry

Part of the book series: Springer Theses ((Springer Theses))

  • 449 Accesses

Abstract

The heme-thiolate enzymes such as cytochrome P450 (CYP), chloroperoxidase (CPO), P450BSβ and recently discovered peroxygenase, AaeAPO, catalyze a variety of crucial oxidative reactions. Among them, the activation of inert hydrocarbons via C–H bond hydroxylation plays an important role in biology. These reactions are involved in the biosynthesis of steroids, the degradation of xenobiotics, the metabolism of drugs and so on. Understanding the mechanisms of these reactions provides us guidelines for the design of new catalysts and the application of biocatalysts to chemical synthesis and drug development. In this chapter, we review the discovery and function of several important heme-thiolate enzymes. Next, the characterization of intermediates in the catalytic cycle during the oxidative reactions is addressed. Finally, applications of the knowledge obtained from these mechanistic investigations on the design of new enzymatic catalysts are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Crabtree, R.H.: Alkane C-H activation and functionalization with homogeneous transition metal catalysts: a century of progress—a new millennium in prospect. J. Chem. Soc. Dalton 2437–2450 (2001)

    Google Scholar 

  2. Dick, A.R., Sanford, M.S.: Transition metal catalyzed oxidative functionalization of carbon-hydrogen bonds. Tetrahedron 62, 2439–2463 (2006)

    Article  CAS  Google Scholar 

  3. Austin, R.N., Groves, J.T.: Alkane-oxidizing metalloenzymes in the carbon cycle. Metallomics 3, 775–787 (2011)

    Article  CAS  Google Scholar 

  4. Groves, J.T.: High-valent iron in chemical and biological oxidations. J. Inorg. Biochem. 100, 434–447 (2006)

    Article  CAS  Google Scholar 

  5. Lewis, J.C., Coelho, P.S., Arnold, F.H.: Enzymatic functionalization of carbon-hydrogen bonds. Chem. Soc. Rev. 40, 2003–2021 (2011)

    Article  CAS  Google Scholar 

  6. Hausinger, R.P.: Fe(II)/α-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. 39, 21–68 (2004)

    Article  CAS  Google Scholar 

  7. Krebs, C., Fujimori, D.G., Walsh, C.T., Bollinger Jr, J.M.: Non-heme Fe(IV)-oxo intermediates. Acc. Chem. Res. 40, 484–492 (2007)

    Article  CAS  Google Scholar 

  8. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L., Rao, A.: Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009)

    Article  CAS  Google Scholar 

  9. Koch, D.J., Chen, M.M., Van Beilen, J.B., Arnold, F.H.: In vivo evolution of butane oxidation by terminal alkane hydroxylases AlkB and CYP153A6. Appl. Environ. Microbiol. 75, 337–344 (2009)

    Article  CAS  Google Scholar 

  10. Smith, C.A., Hyman, M.R.: Oxidation of methyl tert-butyl ether by alkane hydroxylase in dicyclopropylketone-induced and n-octane-grown Pseudomonas putida GPo1. Appl. Environ. Microbiol. 70, 4544–4550 (2004)

    Article  CAS  Google Scholar 

  11. Lipscomb, J.D.: Biochemistry of the soluble methane monooxygenase. Annu. Rev. Microbiol. 48, 371–399 (1994)

    Article  CAS  Google Scholar 

  12. Lieberman, R.L., Rosenzweig, A.C.: Crystal structure of a membrane-bound metalloenzyme that catalyses the biological oxidation of methane. Nature 434, 177–182 (2005)

    Article  CAS  Google Scholar 

  13. Hatcher, L.Q., Karlin, K.D.: Oxidant types in copper-dioxygen chemistry: the ligand coordination defines the Cun-O2 structure and subsequent reactivity. J. Biol. Inorg. Chem. 9, 669–683 (2004)

    Article  CAS  Google Scholar 

  14. Klinman, J.P.: The copper-enzyme family of dopamine β-monooxygenase and peptidylglycine α-hydroxylating monooxygenase: resolving the chemical pathway for substrate hydroxylation. J. Biol. Chem. 281, 3013–3016 (2006)

    Article  CAS  Google Scholar 

  15. Prigge, S.T., Mains, R.E., Eipper, B.A., Amzel, L.M.: New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell. Mol. Life Sci. 57, 1236–1259 (2000)

    Article  CAS  Google Scholar 

  16. Groves, J.T.: In: Ortiz de Montellano, P.R. (ed.) Cytochrome P450: Structure, Mechanism and Biochemistry, 3rd edn. pp. 1–44. Kluwer Academic/Plenum, New York (2004)

    Google Scholar 

  17. Ortiz de Montellano, P.R.: Hydrocarbon hydroxylation by cytochrome P450 enzymes. Chem. Rev. 110, 932–948 (2010)

    Article  CAS  Google Scholar 

  18. Omura, T.: Heme-thiolate proteins. Biochem. Biophys. Res. Co. 338, 404–409 (2005)

    Article  CAS  Google Scholar 

  19. Sono, M., Roach, M.P., Coulter, E.D., Dawson, J.H.: Heme-containing oxygenases. Chem. Rev. 96, 2841–2887 (1996)

    Article  CAS  Google Scholar 

  20. Green, M.T.: C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450. Curr. Opin. Chem. Biol. 13, 84–88 (2009)

    Article  CAS  Google Scholar 

  21. Hsu, M.H., Savas, Ü., Griffin, K.J., Johnson, E.F.: Human cytochrome P450 family 4 enzymes: Function, genetic variation and regulation. Drug Metab. Rev. 39, 515–538 (2007)

    Article  CAS  Google Scholar 

  22. Schlichting, I., Berendzen, J., Chu, K., Stock, A.M., Maves, S.A., Benson, D.E., Sweet, B.M., Ringe, D., Petsko, G.A., Sligar, S.G.: The catalytic pathway of cytochrome P450cam at atomic resolution. Science 287, 1615–1622 (2000)

    Article  CAS  Google Scholar 

  23. Aikens, J., Sligar, S.G.: Kinetic solvent isotope effects during oxygen activation by cytochrome P-450cam. J. Am. Chem. Soc. 116, 1143–1144 (1994)

    Article  CAS  Google Scholar 

  24. Imai, M., Shimada, H., Watanabe, Y., Matsuhima-Hibiya, Y., Makino, R., Koga, H., Horiuchi, T., Ishimura, Y.: Uncoupling of the cytochrome P-450cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: a possible role of the hydroxy amino acid in oxygen activation. Proc. Natl. Acad. Sci. USA 86, 7823–7827 (1989)

    Article  CAS  Google Scholar 

  25. Clutterbuck, P.W., Mukhopadhyay, S.L., Oxford, A.E., Raistrick, H.: Studies in the biochemistry of micro-organisms 65. (A) A survey of chlorine metabolism by moulds (B) Caldariomycin, C5H802Cl2, a metabolic product of Caldariomyces fumago woronichin. Biochem. J. 34, 664–677 (1940)

    Article  CAS  Google Scholar 

  26. Morris, D.R., Hager, L.P.: Chloroperoxidase. I. Isolation and properties of the crystalline glycoprotein. J. Biol. Chem. 241, 1763–1768 (1966)

    CAS  Google Scholar 

  27. Zaks, A., Dodds, D.R.: Chloroperoxidase-catalyzed asymmetric oxidations-substrate-specificity and mechanistic study. J. Am. Chem. Soc. 117, 10419–10424 (1995)

    Article  CAS  Google Scholar 

  28. Dawson, J.H., Sono, M.: Cytochrome P-450 and chloroperoxidase: thiolate-ligated heme enzymes. Spectroscopic determination of their active site structures and mechanistic implications of thiolate ligation. Chem. Rev. 87, 1255–1276 (1987)

    Article  CAS  Google Scholar 

  29. Kühnel, K., Derat, E., Terner, J., Shaik, S., Schlichting, I.: Structure and quantum chemical characterization of chloroperoxidase compound 0, a common reaction intermediate of diverse heme enzymes. Proc. Natl. Acad. Sci. USA 104, 99–104 (2007)

    Article  Google Scholar 

  30. Sundaramoorthy, M., Terner, J., Poulos, T.L.: Stereochemistry of the chloroperoxidase active site: crystallographic and molecular-modeling studies. Chem. Biol. 5, 461–473 (1998)

    Article  CAS  Google Scholar 

  31. Sundaramoorthy, M., Terner, J., Poulos, T.L.: The crystal structure of chloroperoxidase: a heme peroxidase-cytochrome P450 functional hybrid. Structure 3, 1367–1377 (1995)

    Article  CAS  Google Scholar 

  32. Yi, X., Conesa, A., Punt, P.J., Hager, L.P.: Examining the role of glutamic acid 183 in chloroperoxidase catalysis. J. Biol. Chem. 278, 13855–13859 (2003)

    Article  CAS  Google Scholar 

  33. Fujishiro, T., Shoji, O., Nagano, S., Sugimoto, H., Shiro, Y., Watanabe, Y.: Crystal structure of H2O2-dependent cytochrome P450(SP alpha) with its bound fatty acid substrate insight into the regioselective hydroxylation of fatty acids at the alpha position. J. Biol. Chem. 286, 29941–29950 (2011)

    Article  CAS  Google Scholar 

  34. Shoji, O., Fujishiro, T., Nakajima, H., Kim, M., Nagano, S., Shiro, Y., Watanabe, Y.: Hydrogen peroxide dependent monooxygenations by tricking the substrate recognition of cytochrome P450(BS beta). Angew. Chem. Int. Ed. 46, 3656–3659 (2007)

    Article  CAS  Google Scholar 

  35. Lee, D.S., Yamada, A., Sugimoto, H., Matsunaga, I., Ogura, H., Ichihara, K., Adachi, S., Park, S.Y., Shiro, Y.: Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis: crystallographic, spectroscopic, and mutational studies. J. Biol. Chem. 278, 9761–9767 (2003)

    Article  CAS  Google Scholar 

  36. Hofrichter, M., Ullrich, R., Pecyna, M.J., Liers, C., Lundell, T.: New and classic families of secreted fungal heme peroxidases. Appl. Microbiol. Biotechnol. 87, 871–897 (2010)

    Article  CAS  Google Scholar 

  37. Ullrich, R., Nuske, J., Scheibner, K., Spantzel, J., Hofrichter, M.: Novel haloperoxidase from the agaric basidiomycete Agrocybe aegerita oxidizes aryl alcohols and aldehydes. Appl. Environ. Microbiol. 70, 4575–4581 (2004)

    Article  CAS  Google Scholar 

  38. Peter, S., Kinne, M., Wang, X., Ullrich, R., Kayser, G., Groves, J.T., Hofrichter, M.: Selective hydroxylation of alkanes by an extracellular fungal peroxygenase. FEBS J. 278, 3667–3675 (2011)

    Article  CAS  Google Scholar 

  39. Piontek, K., Ullrich, R., Liers, C., Diederichs, K., Plattner, D.A., Hofrichter, M.: Crystallization of a 45 kDa peroxygenase/peroxidase from the mushroom Agrocybe aegerita and structure determination by SAD utilizing only the haem iron. Acta. Crystallogr. F 66, 693–698 (2010)

    Article  CAS  Google Scholar 

  40. Wang, X., Peter, S., Kinne, M., Hofrichter, M., Groves, J.T.: Detection and kinetic characterization of a highly reactive heme-thiolate peroxygenase compound I. J. Am. Chem. Soc. 134, 12897–12900 (2012)

    Article  CAS  Google Scholar 

  41. Luthra, A., Denisov, I.G., Sligar, S.G.: Spectroscopic features of cytochrome P450 reaction intermediates. Arch. Biochem. Biophys. 507, 26–35 (2011)

    Article  CAS  Google Scholar 

  42. Nelson, S.D., Trager, W.F.: The use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome P450-catalyzed reactions, and mechanisms of metabolically dependent toxicity. Drug Metab. Dispos. 31, 1481–1498 (2003)

    Article  CAS  Google Scholar 

  43. Groves, J.T.: The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies. Proc. Natl. Acad. Sci. USA 100, 3569–3574 (2003)

    Article  CAS  Google Scholar 

  44. Jung, C.: The mystery of cytochrome P450 Compound I: a mini-review dedicated to Klaus Ruckpaul. BBA-proteins proteom 1814, 46–57 (2011)

    Article  CAS  Google Scholar 

  45. Sligar, S.G., Makris, T.M., Denisov, I.G.: Thirty years of microbial P450 monooxygenase research: peroxo-heme intermediates: the central bus station in heme oxygenase catalysis. Biochem. Biophys. Res. Co. 338, 346–354 (2005)

    Article  CAS  Google Scholar 

  46. Que, L.J.: Physical methods in bioinorganic chemistry, 1st edn. University Science Books (2000)

    Google Scholar 

  47. Solomon, E.I.; Hodgon, K.O.: Spectroscopic methods in bioinorganic chemistry. American Chemical Society (1998)

    Google Scholar 

  48. Johnson, K.A.: Transient-state kinetic analysis of enzyme reaction pathways. Enzymes XX, 1–61 (1992)

    Google Scholar 

  49. Carrington, A., McLachlan, A.D.: Introduction to magnetic resonance. Harper and Row, New York (1967)

    Google Scholar 

  50. Pilbrow, J.R.: Transition ion electron paramagnetic resonance. Oxford University Press, Oxford (1991)

    Google Scholar 

  51. Gütlich, P., Bill, E., Trautwein, A.X.: Mössbauer spectroscopy and transition metal chemistry. Fundamentals and applications. Springer, Berlin (2011)

    Book  Google Scholar 

  52. Spiro, T.G.: Biological applications of raman spectroscopy, vol. 2. Wiley, Canada (1988)

    Google Scholar 

  53. DeBeer, S.: X-ray absorption spectroscopy. In: Ribbe, M.W. (ed.) Nitrogen fixation: methods and protocols, vol. 766, pp. 165–176 (2011)

    Google Scholar 

  54. Iggo, J.A.: NMR spectroscopy in inorganic chemistry. Oxford University Press, Oxford (2000)

    Google Scholar 

  55. Stephens, P.J.: Theory of magnetic circular dichroism. J. Chem. Phys. 52, 3489–3516 (1970)

    Article  CAS  Google Scholar 

  56. Drenth, J.: Principles of protein X-ray crystallography, 3rd edn. Springer, Berlin (2006)

    Google Scholar 

  57. Schweiger, A., Jeschke, G.: Principles of pulse electron paramagnetic resonance. Oxford (2001)

    Google Scholar 

  58. Hoffmann, E.D., Stroobant, V.: Mass spectrometry: principles and applications. Wiley, New York (2007)

    Google Scholar 

  59. Bard, A.J.: Electrochemical methods: fundamental and applications, 2nd edn. Wiley, New York (2000)

    Google Scholar 

  60. Shaik, S., Cohen, S., Wang, Y., Chen, H., Kumar, D., Thiel, W.: P450 enzymes: their structure, reactivity, and selectivity-modeled by QM/MM calculations. Chem. Rev. 110, 949–1017 (2010)

    Article  CAS  Google Scholar 

  61. Neese, F.: Prediction of molecular properties and molecular spectroscopy with density functional theory: from fundamental theory to exchange-coupling. Coordin. Chem. Rev. 253, 526–563 (2009)

    Article  CAS  Google Scholar 

  62. Davydov, R., Makris, T.M., Kofman, V., Werst, D.E., Sligar, S.G., Hoffman, B.M.: Hydroxylation of camphor by-reduced oxy-cytochrome P450cam: mechanistic implications of EPR and ENDOR studies of catalytic intermediates in native and mutant enzymes. J. Am. Chem. Soc. 123, 1403–1415 (2001)

    Article  CAS  Google Scholar 

  63. Denisov, I.G., Makris, T.M., Sligar, S.G.: Formation and decay of hydroperoxo-ferric heme complex in horseradish peroxidase studied by cryoradiolysis. J. Biol. Chem. 277, 42706–42710 (2002)

    Article  CAS  Google Scholar 

  64. Denisov, I.G., Dawson, J.H., Hager, L.P., Sligar, S.G.: The ferric-hydroperoxo complex of chloroperoxidase. Biochem. Biophys. Res. Co. 363, 954–958 (2007)

    Article  CAS  Google Scholar 

  65. Denisov, I.G., Makris, T.M., Sligar, S.G.: Cryotrapped reaction intermediates of cytochrome P450 studied by radiolytic reduction with phosphorus-32. J. Biol. Chem. 276, 11648–11652 (2001)

    Article  CAS  Google Scholar 

  66. Egawa, T., Shimada, H., Ishimura, Y.: Evidence for compound I formation in the reaction of cytochrome-P450cam with M-chloroperbenzoic acid. Biochem. Biophys. Res. Co. 201, 1464–1469 (1994)

    Article  CAS  Google Scholar 

  67. Rittle, J., Green, M.T.: Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330, 933–937 (2010)

    Article  CAS  Google Scholar 

  68. Stone, K.L., Behan, R.K., Green, M.T.: X-ray absorption spectroscopy of chloroperoxidase compound I: Insight into the reactive intermediate of P450 chemistry. Proc. Natl. Acad. Sci. USA 102, 16563–16565 (2005)

    Article  CAS  Google Scholar 

  69. Egawa, T., Miki, H., Ogura, T., Makino, R., Ishimura, Y., Kitagawa, T.: Observation of the Fe(IV)=O stretching Raman band for a thiolate-ligated heme protein. Compound I of chloroperoxidase. FEBS Lett. 305, 206–208 (1992)

    Article  CAS  Google Scholar 

  70. Davydov, R., Dawson, J.H., Perera, R., Hoffman, B.M.: The use of deuterated camphor as a substrate in 1H ENDOR studies of hydroxylation by cryoreduced oxy P450cam provides new evidence of the involvement of compound I. Biochemistry 52, 667–671 (2013)

    Article  CAS  Google Scholar 

  71. Groves, J.T., Gross, Z., Stern, M.K.: Preparation and reactivity of oxoiron(IV) porphyrins. Inorg. Chem. 33, 5065–5072 (1994)

    Article  CAS  Google Scholar 

  72. Behan, R.K., Hoffart, L.M., Stone, K.L., Krebs, C., Green, M.T.: Evidence for basic ferryls in cytochromes P450. J. Am. Chem. Soc. 128, 11471–11474 (2006)

    Article  CAS  Google Scholar 

  73. Green, M.T., Dawson, J.H., Gray, H.B.: Oxoiron(IV) in chloroperoxidase compound II is basic: implications for P450 chemistry. Science 304, 1653–1656 (2004)

    Article  CAS  Google Scholar 

  74. Nam, W., Park, S.E., Lim, I.K., Lim, M.H., Hong, J., Kim, J.: First direct evidence for stereospecific olefin epoxidation and alkane hydroxylation by an oxoiron(IV) porphyrin complex. J. Am. Chem. Soc. 125, 14674–14675 (2003)

    Article  CAS  Google Scholar 

  75. Newcomb, M., Halgrimson, J.A., Horner, J.H., Wasinger, E.C., Chen, L.X., Sligar, S.G.: X-ray absorption spectroscopic characterization of a cytochrome P450 compound II derivative. Proc. Natl. Acad. Sci. USA 105, 8179–8184 (2008)

    Article  CAS  Google Scholar 

  76. Stone, K.L., Behan, R.K., Green, M.T.: Resonance Raman spectroscopy of chloroperoxidase compound II provides direct evidence for the existence of an iron(IV)-hydroxide. Proc. Natl. Acad. Sci. USA 103, 12307–12310 (2006)

    Article  CAS  Google Scholar 

  77. Mayer, J.M.: Hydrogen atom abstraction by metal-oxo complexes: understanding the analogy with organic radical reactions. Acc. Chem. Res. 31, 441–450 (1998)

    Article  CAS  Google Scholar 

  78. Griller, D., Ingold, K.U.: Free-radical clocks. Acc. Chem. Res. 13, 317–323 (1980)

    Article  CAS  Google Scholar 

  79. Groves, J.T., Kruper, W.J., Haushalter, R.C.: Hydrocarbon oxidations with oxometalloporphinates: isolation and reactions of a (porphinato)manganese(V) complex. J. Am. Chem. Soc. 102, 6375–6377 (1980)

    Article  CAS  Google Scholar 

  80. Ortiz de Montellano, P.R., Stearns, R.A.: Timing of the radical recombination step in cytochrome-P-450 catalysis with ring-strained probes. J. Am. Chem. Soc. 109, 3415–3420 (1987)

    Article  CAS  Google Scholar 

  81. Auclair, K., Hu, Z.B., Little, D.M., Ortiz de Montellano, P.R., Groves, J.T.: Revisiting the mechanism of P450 enzymes with the radical clocks norcarane and spiro[2,5]octane. J. Am. Chem. Soc. 124, 6020–6027 (2002)

    Article  CAS  Google Scholar 

  82. Austin, R.N., Deng, D.Y., Jiang, Y.Y., Luddy, K., van Beilen, J.B., Ortiz de Montellano, P.R., Groves, J.T.: The diagnostic substrate bicyclohexane reveals a radical mechanism for bacterial cytochrome P450 in whole cells. Angew. Chem. Int. Ed. 45, 8192–8194 (2006)

    Article  CAS  Google Scholar 

  83. Newcomb, M., Toy, P.H.: Hypersensitive radical probes and the mechanisms of cytochrome P450-catalyzed hydroxylation reactions. Acc. Chem. Res. 33, 449–455 (2000)

    Article  CAS  Google Scholar 

  84. Bowry, V.W., Ingold, K.U.: A radical clock investigation of microsomal cytochrome P-450 hydroxylation of hydrocarbons. Rate of oxygen rebound. J. Am. Chem. Soc. 113, 5699–5707 (1991)

    Article  CAS  Google Scholar 

  85. Cooper, H.L.R., Groves, J.T.: Molecular probes of the mechanism of cytochrome P450. Oxygen traps a substrate radical intermediate. Arch. Biochem. Biophys. 507, 111–118 (2011)

    Article  CAS  Google Scholar 

  86. Toy, P.H., Newcomb, M., Hollenberg, P.F.: Hypersensitive mechanistic probe studies of cytochrome P450-catalyzed hydroxylation reactions. Implications for the cationic pathway. J. Am. Chem. Soc. 120, 7719–7729 (1998)

    Article  CAS  Google Scholar 

  87. Iyer, K.R., Jones, J.P., Darbyshire, J.F., Trager, W.F.: Intramolecular isotope effects for benzylic hydroxylation of isomeric xylenes and 4,4′-dimethylbiphenyl by cytochrome P450: relationship between distance of methyl groups and masking of the intrinsic isotope effect. Biochemistry 36, 7136–7143 (1997)

    Article  CAS  Google Scholar 

  88. Cleland, W.W.: Use of isotope effects to elucidate enzyme mechanisms. CRC Cr. Rev. Bioch. Mol. 13, 385–428 (1982)

    Article  CAS  Google Scholar 

  89. Bordeaux, M., Galarneau, A., Drone, J.: Catalytic, mild, and selective oxyfunctionalization of linear alkanes: current challenges. Angew. Chem. Int. Ed. 51, 10712–10723 (2012)

    Article  CAS  Google Scholar 

  90. O’Reilly, E., Köhler, V., Flitsch, S.L., Turner, N.J.: Cytochromes P450 as useful biocatalysts: addressing the limitations. Chem. Commun. 47, 2490–2501 (2011)

    Article  Google Scholar 

  91. Jung, S.T., Lauchli, R., Arnold, F.H.: Cytochrome P450: taming a wild type enzyme. Curr. Opin. Biotech. 22, 809–817 (2011)

    Article  CAS  Google Scholar 

  92. Fowler, S.M., England, P.A., Westlake, A.C.G., Rouch, D.R., Nickerson, D.P., Blunt, C., Braybrook, D., West, S., Wong, L.L., Flitsch, S.L.: Cytochrome P-450 cam monooxygenase can be redesigned to catalyse the regioselective aromatic hydroxylation of diphenylmethane. J. Chem. Soc. Chem. Comm. 2761–2762 (1994)

    Google Scholar 

  93. Bell, S.G., Orton, E., Boyd, H., Stevenson, J.A., Riddle, A., Campbell, S., Wong, L.L.: Engineering cytochrome P450cam into an alkane hydroxylase. Dalton T. 11, 2133–2140 (2003)

    Article  Google Scholar 

  94. Meinhold, P., Peters, M.W., Hartwick, A., Hernandez, A.R., Arnold, F.H.: Engineering cytochrome P450BM3 for terminal alkane hydroxylation. Adv. Synth. Catal. 348, 763–772 (2006)

    Article  CAS  Google Scholar 

  95. Romero, P.A., Arnold, F.H.: Exploring protein fitness landscapes by directed evolution. Nat. Rev. Mol. Cell Biol. 10, 866–876 (2009)

    Article  CAS  Google Scholar 

  96. Meinhold, P., Peters, M.W., Chen, M.M.Y., Takahashi, K., Arnold, F.H.: Direct conversion of ethane to ethanol by engineered cytochrome P450 BM3. Chem. Biol. Chem. 6, 1765–1768 (2005)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Philadelphia, PA, USA

    Xiaoshi Wang

Authors
  1. Xiaoshi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoshi Wang .

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Wang, X. (2016). Hydrocarbon Oxygenation by Heme-Thiolate Enzymes . In: A Novel Heme-Thiolate Peroxygenase AaeAPO and Its Implications for C-H Activation Chemistry. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-319-03236-8_1

Download citation

Publish with us

Policies and ethics

Search

Navigation