Abstract
Over sixty years ago, scientists identified microorganisms capable of oxidizing alkanes and other hydrocarbons, including methane[1]. Since then, many of these microorganisms have been discovered[2] and the various metalloenzymes (responsible for activating these C-H bonds) present in these microorganisms have been extensively studied[3]. These enzymes are able to carry out oxidation reactions by reductive activation of dioxygen or S-Adenosylmethionine (SAM) under very mild conditions (atmospheric pressures, ambient temperature, in aqueous media), thanks to the presence of a metal center in their active site. On the other hand, shadows still hang over their operating mechanism, but the development of increasingly advanced spectroscopic methods (Raman, Mössbauer, EPR, magnetic circular dichroism, protein crystallography) is enabling us to gradually provide answers to the questions that remain unanswered.
As part of this seminar series, my presentation focused on the catalytic activation of C-H bonds by iron metalloenzymes. This is a central theme in bioinorganic chemistry, and two main families of enzymes were discussed. Enzymes belonging to the Radical-SAM family, whose active species is produced by the monoelectronic reduction of S-Adenosylmethionine catalyzed by a [4Fe-4S] center. Enzymes belonging to the family of proteins containing a binuclear non-heme iron center, whose oxidizing species derives from the reductive activation of oxygen by the metal center. For both enzyme families, the focus has been on enzymes catalyzing reactions on tRNA or protein substrates [4, 7].
References
[1] Higgins I.J., Best D.J., Hammond R.C. and Scott D., " Methane-oxidizing microorganisms ". Microbiological Reviews, vol. 45, 1981, pp. 556-590, https://doi.org/10.1128/mr.45.4.556-590.1981.
[2] Kelly D.P., Anthony C. and Murrell J.C., " Insights into the obligate methanotroph Methylococcus capsulatus ", Trends in Microbiology, vol. 13,no. 5, 2005, pp. 195-198, http://dx.doi.org/10.1016/j.tim.2005.03.003.
[3] Merkx M., Kopp D.A., Sazinsky M.H., Blazyk J.L., Müller J. and Lippard S.J., " Dioxygen activation and methane hydroxylation by soluble methane monooxygenase: A tale of two irons and three proteins ", Angewandte Chemie International Edition, vol. 40,no. 15, 2001, pp. 2782-2807, https://doi.org/10.1002/1521-3773(20010803)40:152782::AID-ANIE2782>3.0.CO;2-P.
[4] Atta M., Mulliez E., Arragain S., Forouhar F., Hunt J.F. and Fontecave M., " S-adenosylmethionine-dependent radical-based modification of biological macromolecules ", Current Opinion in Structural Biology, vol. 20,no. 6, 2010, pp. 684-692, https://doi.org/10.1016/j.sbi.2010.09.009.
[5] Fontecave M., Atta M. and Mulliez E., " S-adenosylmethionine: nothing goes to waste ", Trends in Biochemical Sciences, vol. 29,no. 5, 2004, pp. 243-249, https://doi.org/10.1016/j.tibs.2004.03.007.
[6] Mathevon C., Pierrel F., Oddou J.-L., Garcia-Serres R., Blondin G., Latour J.-M., Ménage S., Gambarelli S., Fontecave M. and Atta M., " tRNA-modifying MiaE protein from Salmonella typhimurium is a nonheme diiron monooxygenase ", Proceedings of the National Academy of Sciences, vol. 104,no. 33, 2007, pp. 13295-13300, https://doi.org/10.1073/pnas.0704338104.
[7] Atta M., Arragain S., Fontecave M., Mulliez E., Hunt J.F., Luff J.D. and Forouhar F., " The methylthiolation reaction mediated by the Radical-SAM enzymes ", Biochimica et Biophysica Acta, vol. 1824,no. 11, 2012, pp. 1223-1230, https://doi.org/10.1016/j.bbapap.2011.11.007.
