The oxidative cleavage of alkenes is classically performed by chemical methods, although they display several drawbacks. Ozonolysis requires harsh conditions (？78°C, for a safe process) and reducing reagents in a molar amount, whereas the use of poisonous heavy metals such as Cr, Os, or Ru as catalysts is additionally plagued by low yield and selectivity. Conversely, heme and nonheme enzymes can catalyse the oxidative alkene cleavage at ambient temperature and atmospheric pressure in an aqueous buffer, showing excellent chemo- and regioselectivities in certain cases. This paper focuses on the alkene cleavage catalysed by iron cofactor-dependent enzymes encompassing the reaction mechanisms (in case where it is known) and the application of these enzymes in biocatalysis. 1. Introduction The oxidative cleavage of alkenes is a widely employed method in synthetic chemistry, particularly to introduce oxygen functionalities into molecules, remove protecting groups, and degrade large molecules. Moreover, the synthesis of a large amount of bioactive compounds involves the alkene cleavage as a key step. Ozonolysis is the most employed chemical method for cleaving alkenes since it is considered the most efficient and cleanest. However, the ozonolysis requires harsh conditions such as low temperature (ca. ？78°C), hence imposing the use of a special equipment (e.g., ozoniser) and reducing reagents in molar amounts during the workup [1]. Furthermore, safety hazards complicate this reaction on large scale, and serious accidents from explosion have been reported [2, 3]. Alternative protocols envisage the use of poisonous heavy metals such as Cr, Os, or Ru which are plagued by mediocre yields and selectivities [4–6]. Conversely, enzymes can activate the most innocuous oxidant, that is, molecular oxygen, and catalyse the alkene cleavage at ambient temperature and atmospheric pressure in aqueous buffer. Besides, in certain cases enzymes are capable to cleave olefinic functionalities in high chemo- and regioselective fashion allowing biocatalysis to compete with chemical methods [7–9]. Otherwise, the rising popularity of natural products during the last decade has triggered off remarkable research activities regarding the use of biocatalysis for the production of flavour compounds [10]. In fact, products derived from the bioprocess of natural substrates (i.e., using wild-type microorganisms or isolated enzymes thereof) are defined as natural. The tag natural was one of the main reasons for seeking biochemical routes to high-priced natural flavours such as vanillin, and
References
[1]
R. A. Berglund, Encyclopedia of Reagents for Organic Synthesis, vol. 6, Wiley, New York, NY, USA, 1995.
[2]
K. Koike, G. Inoue, and T. Fukuda, “Explosion hazard of gaseous ozone,” Journal of Chemical Engineering of Japan, vol. 32, no. 3, pp. 295–299, 1999.
[3]
R. A. Ogle and J. L. Schumacher, “Investigation of an explosion and flash fire in a fixed bed reactor,” Process Safety Progress, vol. 17, no. 2, pp. 127–133, 1998.
[4]
J. March, Advanced Organic Chemistry. Reactions, Mechanisms and Structures, Wiley, New York, NY, USA, 4th edition, 1992.
[5]
P. Y. Bruice, Organic Chemistry. International Edition, Pearson Education, Upper Saddle River, NJ, USA, 4th edition, 2004.
[6]
R. U. Lemieux and E. Von Rudloff, “Periodate-permanganate oxidations: I. Oxidation of olefins,” Canadian Journal of Chemistry, vol. 33, no. 11, pp. 1701–1709, 1955.
[7]
C. E. Paul, A. Rajagopalan, I. Lavandera, V. Gotor-Fernandez, W. Kroutil, and V. Gotor, “Expanding the regioselective enzymatic repertoire: oxidative mono-cleavage of dialkenes catalyzed by Trametes hirsuta,” Chemical Communications, vol. 48, no. 27, pp. 3303–3305, 2012.
[8]
M. Lara, F. G. Mutti, S. M. Glueck, and W. Kroutil, “Biocatalytic cleavage of alkenes with O2 and Trametes hirsuta G FCC 047,” European Journal of Organic Chemistry, no. 21, pp. 3668–3672, 2008.
[9]
M. Lara, F. G. Mutti, S. M. Glueck, and W. Kroutil, “Oxidative enzymatic alkene cleavage: indications for a nonclassical enzyme mechanism,” Journal of the American Chemical Society, vol. 131, no. 15, pp. 5368–5369, 2009.
[10]
J. Schrader, M. M. W. Etschmann, D. Sell, J. M. Hilmer, and J. Rabenhorst, “Applied biocatalysis for the synthesis of natural flavour compounds-current industrial processes and future prospects,” Biotechnology Letters, vol. 26, no. 6, pp. 463–472, 2004.
[11]
W. Adam, M. Lazarus, C. R. Saha-Moller, et al., “Biotransformations with peroxidases,” in Advanced in Biochemical Engineering/Biotechnology, T. Sheper, Ed., vol. 63, pp. 73–108, Springer-Verlag, Berlin, Germany, 1999.
[12]
G. I. Berglund, G. H. Carlsson, A. T. Smith, H. Sz？ke, A. Henriksen, and J. Hajdu, “The catalytic pathway of horseradish peroxidase at high resolution,” Nature, vol. 417, no. 6887, pp. 463–468, 2002.
[13]
I. Schlichting, J. Berendzen, K. Chu et al., “The catalytic pathway of cytochrome P450cam at atomic resolution,” Science, vol. 287, no. 5458, pp. 1615–1622, 2000.
[14]
G. Cilento and W. Adam, “From free radicals to electronically excited species,” Free Radical Biology and Medicine, vol. 19, no. 1, pp. 103–114, 1995.
[15]
P. D. Shaw and L. P. Hager, “Biological Chlorination: VI: chloroperoxidase: a component of the β-ketoadipate chlorinase system,” Journal of Biological Chemistry, vol. 236, no. 6, pp. 1626–1630, 1961.
[16]
L. P. Hager, D. R. Morris, F. S. Brown, and H. Eberwein, “Chloroperoxidase. II. Utilization of halogen anions,” Journal of Biological Chemistry, vol. 241, no. 8, pp. 1769–1777, 1966.
[17]
J. A. Thomas, D. R. Morris, and L. P. Hager, “Chloroperoxidase. VII. Classical peroxidatic, catalatic, and halogenating forms of the enzyme,” Journal of Biological Chemistry, vol. 245, no. 12, pp. 3129–3134, 1970.
[18]
A. Zaks and D. R. Dodds, “Chloroperoxidase-catalyzed asymmetric oxidations: substrate specificity and mechanistic study,” Journal of the American Chemical Society, vol. 117, no. 42, pp. 10419–10424, 1995.
[19]
M. P. J. Van Deurzen, F. Van Rantwijk, and R. A. Sheldon, “Selective oxidations catalyzed by peroxidases,” Tetrahedron, vol. 53, no. 39, pp. 13183–13220, 1997.
[20]
S. Colonna, N. Gaggero, C. Richelmi, and P. Pasta, “Recent biotechnological developments in the use of peroxidases,” Trends in Biotechnology, vol. 17, no. 4, pp. 163–168, 1999.
[21]
S. R. Blanke and L. P. Hager, “Identification of the fifth axial heme ligand of chloroperoxidase,” Journal of Biological Chemistry, vol. 263, no. 35, pp. 18739–18743, 1988.
[22]
P. R. Ortiz De Montellano, Y. S. Choe, G. DePillis, and C. E. Catalano, “Structure-mechanism relationships in hemoproteins. Oxygenations catalyzed by chloroperoxidase and horseradish peroxidase,” Journal of Biological Chemistry, vol. 262, no. 24, pp. 11641–11646, 1987.
[23]
J. Geigert, T. D. Lee, D. J. Dalietos, D. S. Hirano, and S. L. Neidleman, “Epoxidation of alkenes by chloroperoxidase catalysis,” Biochemical and Biophysical Research Communications, vol. 136, no. 2, pp. 778–782, 1986.
[24]
E. J. Allain, L. P. Hager, L. Deng, and E. N. Jacobsen, “Highly enantioselective epoxidation of disubstituted alkenes with hydrogen peroxide catalyzed by chloroperoxidase,” Journal of the American Chemical Society, vol. 115, no. 10, pp. 4415–4416, 1993.
[25]
D. J. Bougioukou and I. Smonou, “Chloroperoxidase-catalyzed oxidation of conjugated dienoic esters,” Tetrahedron Letters, vol. 43, no. 2, pp. 339–342, 2002.
[26]
D. J. Bougioukou and I. Smonou, “Mixed peroxides from the chloroperoxidase-catalyzed oxidation of conjugated dienoic esters with a trisubstituted terminal double bond,” Tetrahedron Letters, vol. 43, no. 25, pp. 4511–4514, 2002.
[27]
W. Chamulitrat, N. Takahashi, and R. P. Mason, “Peroxyl, alkoxyl, and carbon-centered radical formation from organic hydroperoxides by chloroperoxidase,” Journal of Biological Chemistry, vol. 264, no. 14, pp. 7889–7899, 1989.
[28]
M. Gajhede, D. J. Schuller, A. Henriksen, A. T. Smith, and T. L. Poulos, “Crystal structure of horseradish peroxidase C at 2.15 ？ resolution,” Nature Structural Biology, vol. 4, no. 12, pp. 1032–1038, 1997.
[29]
P. R. Ortiz De Montellano and L. A. Grab, “Cooxidation of styrene by horseradish peroxidase and phenols: a biochemical model for protein-mediated cooxidation,” Biochemistry, vol. 26, no. 17, pp. 5310–5314, 1987.
[30]
S.-I. Ozaki and P. R. Ortiz De Montellano, “Molecular engineering of horseradish peroxidase: thioether sulfoxidation and styrene epoxidation by Phe-41 leucine and threonine mutants,” Journal of the American Chemical Society, vol. 117, no. 27, pp. 7056–7064, 1995.
[31]
K. Q. Ling and L. M. Sayre, “Horseradish peroxidase-mediated aerobic and anaerobic oxidations of 3-alkylindoles,” Bioorganic and Medicinal Chemistry, vol. 13, no. 10, pp. 3543–3551, 2005.
[32]
F. G. Mutti, M. Lara, M. Kroutil, and W. Kroutil, “Ostensible enzyme promiscuity: alkene cleavage by peroxidases,” Chemistry, vol. 16, no. 47, pp. 14142–14148, 2010.
[33]
A. Tuynman, J. L. Spelberg, I. M. Kooter, H. E. Schoemaker, and R. Wever, “Enantioselective epoxidation and carbon-carbon bond cleavage catalyzed by Coprinus cinereus peroxidase and myeloperoxidase,” Journal of Biological Chemistry, vol. 275, no. 5, pp. 3025–3030, 2000.
[34]
U. T. Bornscheuer and R. J. Kazlauskas, “Catalytic promiscuity in biocatalysis: using old enzymes to form new bonds and follow new pathways,” Angewandte Chemie, vol. 43, no. 45, pp. 6032–6040, 2004.
[35]
K. Hult and P. Berglund, “Enzyme promiscuity: mechanism and applications,” Trends in Biotechnology, vol. 25, no. 5, pp. 231–238, 2007.
[36]
P. J. O'Brien and D. Herschlag, “Catalytic promiscuity and the evolution of new enzymatic activities,” Chemistry and Biology, vol. 6, no. 4, pp. R91–R105, 1999.
[37]
M. Sono, M. P. Roach, E. D. Coulter, and J. H. Dawson, “Heme-containing oxygenases,” Chemical Reviews, vol. 96, no. 7, pp. 2841–2887, 1996.
[38]
S. G. Cady and M. Sono, “1-methyl-DL-tryptophan, β-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and β-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase,” Archives of Biochemistry and Biophysics, vol. 291, no. 2, pp. 326–333, 1991.
[39]
N. Chauhan, S. J. Thackray, S. A. Rafice et al., “Reassessment of the reaction mechanism in the heme dioxygenases,” Journal of the American Chemical Society, vol. 131, no. 12, pp. 4186–4187, 2009.
[40]
N. Chauhan, J. Basran, I. Efimov et al., “The role of serine 167 in human indoleamine 2,3-dioxygenase: a comparison with tryptophan 2,3-dioxygenase,” Biochemistry, vol. 47, no. 16, pp. 4761–4769, 2008.
[41]
S. J. Thackray, C. Bruckmann, J. L. R. Anderson et al., “Histidine 55 of tryptophan 2,3-dioxygenase is not an active site base but regulates catalysis by controlling substrate binding,” Biochemistry, vol. 47, no. 40, pp. 10677–10684, 2008.
[42]
G. Yagil, “The proton dissociation constant of pyrrole, indole and related compounds,” Tetrahedron, vol. 23, no. 6, pp. 2855–2861, 1967.
[43]
I. Efimov, J. Basran, S. J. Thackray, S. Handa, C. G. Mowat, and E. L. Raven, “Structure and reaction mechanism in the heme dioxygenases,” Biochemistry, vol. 50, no. 14, pp. 2717–2724, 2011.
[44]
J. Basran, I. Efimov, N. Chauhan et al., “The mechanism of formation of N-formylkynurenine by heme dioxygenases,” Journal of the American Chemical Society, vol. 133, no. 40, pp. 16251–16257, 2011.
[45]
A. Lewis-Ballester, D. Batabyal, T. Egawa et al., “Evidence for a ferryl intermediate in a heme-based dioxygenase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 41, pp. 17371–17376, 2009.
[46]
L. W. Chung, X. Li, H. Sugimoto, Y. Shiro, and K. Morokuma, “ONIOM study on a missing piece in our understanding of heme chemistry: bacterial tryptophan 2,3-dioxygenase with dual oxidants,” Journal of the American Chemical Society, vol. 132, no. 34, pp. 11993–12005, 2010.
[47]
T. D. H. Bugg and C. J. Winfield, “Enzymatic cleavage of aromatic rings: mechanistic aspects of the catechol dioxygenases and later enzymes of bacterial oxidative cleavage pathways,” Natural Product Reports, vol. 15, no. 5, pp. 513–530, 1998.
[48]
O. Hayaishi, M. Katagiri, and S. Rothberg, “Mechanism of the pyrocatechase reaction,” Journal of the American Chemical Society, vol. 77, no. 20, pp. 5450–5451, 1955.
[49]
O. Hayaishi, “Crystalline oxygenases of pseudomonads,” Bacteriological Reviews, vol. 30, no. 4, pp. 720–731, 1966.
[50]
R. J. Mayer and L. Que, “18O studies of pyrogallol cleavage by catechol 1,2-dioxygenase,” Journal of Biological Chemistry, vol. 259, no. 21, pp. 13056–13060, 1984.
[51]
E. L. Spence, G. J. Langley, and T. D. H. Bugg, “Cis-trans isomerization of a cyclopropyl radical trap catalyzed by extradiol catechol dioxygenases: evidence for a semiquinone intermediate,” Journal of the American Chemical Society, vol. 118, no. 35, pp. 8336–8343, 1996.
[52]
F. H. Vaillancourt, C. J. Barbosa, T. G. Spiro et al., “Definitive evidence for monoanionic binding of 2,3-dihydroxybiphenyl to 2,3-dihydroxybiphenyl 1,2-dioxygenase from UV resonance Raman spectroscopy, UV/Vis absorption spectroscopy, and crystallography,” Journal of the American Chemical Society, vol. 124, no. 11, pp. 2485–2496, 2002.
[53]
J. Sanvoisin, G. J. Langley, and T. D. H. Bugg, “Mechanism of extradiol catechol dioxygenases: evidence for a lactone intermediate in the 2,3-dihydroxyphenylpropionate 1,2-dioxygenase reaction,” Journal of the American Chemical Society, vol. 117, no. 29, pp. 7836–7837, 1995.
[54]
D. P. Kloer and G. E. Schulz, “Structural and biological aspects of carotenoid cleavage,” Cellular and Molecular Life Sciences, vol. 63, no. 19-20, pp. 2291–2303, 2006.
[55]
M. E. Auldridge, D. R. McCarty, and H. J. Klee, “Plant carotenoid cleavage oxygenases and their apocarotenoid products,” Current Opinion in Plant Biology, vol. 9, no. 3, pp. 315–321, 2006.
[56]
E. K. Marasco, K. Vay, and C. Schmidt-Dannert, “Identification of carotenoid cleavage dioxygenases from Nostoc sp. PCC 7120 with different cleavage activities,” Journal of Biological Chemistry, vol. 281, no. 42, pp. 31583–31593, 2006.
[57]
J. A. Olson and O. Hayaishi, “The enzymatic cleavage of beta-carotene into vitamin A by soluble enzymes of rat liver and intestine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 54, no. 5, pp. 1364–1370, 1965.
[58]
M. G. Leuenberger, C. Engeloch-Jarret, and W. D. Woggon, “The reaction mechanism of the enzyme-catalyzed central cleavage of β-carotene to retinal,” Angewandte Chemie, vol. 40, no. 14, pp. 2614–2617, 2001.
[59]
A. During and E. H. Harrison, “Intestinal absorption and metabolism of carotenoids: insights from cell culture,” Archives of Biochemistry and Biophysics, vol. 430, no. 1, pp. 77–88, 2004.
[60]
H. Schmidt, R. Kurtzer, W. Eisenreich, and W. Schwab, “The carotenase AtCCD1 from Arabidopsis thaliana is a dioxygenase,” Journal of Biological Chemistry, vol. 281, no. 15, pp. 9845–9851, 2006.
[61]
D. P. Kloer, S. Ruch, S. Al-Babili, P. Beyer, and G. E. Schulz, “The structure of a retinal-forming carotenoid oxygenase,” Science, vol. 308, no. 5719, pp. 267–269, 2005.
[62]
T. Borowski, M. R. A. Blomberg, and P. E. M. Siegbahn, “Reaction mechanism of apocarotenoid oxygenase (ACO): a DFT study,” Chemistry, vol. 14, no. 7, pp. 2264–2276, 2008.
[63]
E. K. Marasco and C. Schmidt-Dannert, “Identification of bacterial carotenoid cleavage dioxygenase homologues that cleave the interphenyl α,β double bond of stilbene derivatives via a monooxygenase reaction,” ChemBioChem, vol. 9, no. 9, pp. 1450–1461, 2008.
[64]
M. Schilling, F. Patett, W. Schwab, and J. Schrader, “Influence of solubility-enhancing fusion proteins and organic solvents on the in vitro biocatalytic performance of the carotenoid cleavage dioxygenase AtCCD1 in a micellar reaction system,” Applied Microbiology and Biotechnology, vol. 75, no. 4, pp. 829–836, 2007.
[65]
C. Nacke and J. Schrader, “Micelle based delivery of carotenoid substrates for enzymatic conversion in aqueous media,” Journal of Molecular Catalysis B, vol. 77, pp. 67–73, 2012.
[66]
S. Kamoda, N. Habu, M. Samejima, and T. Yoshimoto, “Purification and some properties of lignostilbene-α,β-dioxygenase responsible for the C(α)-C(β) cleavage of a diarylpropane type lignin model compound from Pseudomonas sp. TMY1009,” Agricultural and Biological Chemistry, vol. 53, no. 10, pp. 2757–2761, 1989.
[67]
S. Kamoda, T. Terada, and Y. Saburi, “A common structure of substrate shared by lignostilbenedioxygenase isozymes from Sphingomonas paucimobilis TMY1009,” Bioscience, Biotechnology and Biochemistry, vol. 67, no. 6, pp. 1394–1396, 2003.
[68]
S. Kamoda and Y. Saburi, “Structural and enzymatical comparison of lignostilbene-alpha,beta-dioxygenase isozymes, I, II, and III, from Pseudomonas paucimobilis TMY1009,” Bioscience, Biotechnology, and Biochemistry, vol. 57, no. 6, pp. 931–934, 1993.
[69]
A. Makoto, A. Niwa, S. Kamoda, and Y. Saburi, “Reactivity and stability of Lignostilbene-α, β-dioxygenase-I in various pHs, temperatures, and in aqueous organic solvents,” Journal of Microbiology and Biotechnology, vol. 11, no. 5, pp. 884–886, 2001.
[70]
M. Yamada, Y. Okada, T. Yoshida, and T. Nagasawa, “Purification, characterization and gene cloning of isoeugenol-degrading enzyme from Pseudomonas putida IE27,” Archives of Microbiology, vol. 187, no. 6, pp. 511–517, 2007.
[71]
R. Braaz, P. Fischer, and D. Jendrossek, “Novel type of heme-dependent oxygenase catalyzes oxidative cleavage of rubber (poly-cis-1,4-isoprene),” Applied and Environmental Microbiology, vol. 70, no. 12, pp. 7388–7395, 2004.
[72]
R. Braaz, W. Armbruster, and D. Jendrossek, “Heme-dependent rubber oxygenase RoxA of Xanthomonas sp. cleaves the carbon backbone of poly(cis-1,4-isoprene) by a dioxygenase mechanism,” Applied and Environmental Microbiology, vol. 71, no. 5, pp. 2473–2478, 2005.
[73]
G. Bourel, J. M. Nicaud, B. Nthangeni, P. Santiago-Gomez, J. M. Belin, and F. Husson, “Fatty acid hydroperoxide lyase of green bell pepper: cloning in Yarrowia lipolytica and biogenesis of volatile aldehydes,” Enzyme and Microbial Technology, vol. 35, no. 4, pp. 293–299, 2004.
[74]
G. D. Straganz, H. Hofer, W. Steiner, and B. Nidetzky, “Electronic substituent effects on the cleavage specificity of a non-heme Fe2+-dependent β-diketone dioxygenase and their mechanistic implications,” Journal of the American Chemical Society, vol. 126, no. 39, pp. 12202–12203, 2004.
