10.1002/anie.202103437
Angewandte Chemie International Edition
RESEARCH ARTICLE
the most positive redox potential of all the ligands tested,
facilitating direct reaction with EDA in the absence of reductant.
In contrast, 3ThiA and 4ThzA, which were previously proposed as
isosteric histidine analogues, fail to coordinate the myoglobin
heme iron via their heterocyclic sulfur atom and are hence poor
His93 surrogates. Nevertheless, other metal centers may prove
more tolerant to the NS substitution; 4ThzA could also be an
attractive replacement for histidines that coordinate metal ions via
Nδ rather than Nε. In the future, genetically encoded ligand
exchanges in heme and non-heme iron enzymes, copper binding
enzymes, and many other metalloproteins can be expected to
become as routine as altering the coordination sphere of synthetic
transition metal complexes as a means of rationally tuning metal
ion reactivity.
[18] K. Oohora, H. Meichin, L. Zhao, M. W. Wolf, A. Nakayama, J.
Hasegawa, N. Lehnert, T. Hayashi, J. Am. Chem. Soc. 2017, 139,
17265–17268.
[19] A. Bhagi-Damodaran, I. D. Petrik, N. M. Marshall, H. Robinson, Y. Lu,
J. Am. Chem. Soc. 2014, 136, 11882–11885.
[20] E. J. Moore, V. Steck, P. Bajaj, R. Fasan, J. Org. Chem. 2018, 83,
7480–7490.
[21] D. M. Carminati, R. Fasan, ACS Catal. 2019, 9, 9683–9697.
[22] J. W. Chin, Nature 2017, 550, 53–60.
[23] I. Drienovská, G. Roelfes, Nat. Catal. 2020, 3, 193–202.
[24] A. P. Green, T. Hayashi, P. R. E. Mittl, D. Hilvert, J. Am. Chem. Soc.
2016, 138, 11344–11352.
[25] M. Ortmayer, K. Fisher, J. Basran, E. M. Wolde-Michael, D. J. Heyes,
C. Levy, S. L. Lovelock, J. L. R. Anderson, E. L. Raven, S. Hay, S. E. J.
Rigby, A. P. Green, ACS Catal. 2020, 10, 2735–2746.
[26] M. Pott, T. Hayashi, T. Mori, P. R. E. Mittl, A. P. Green, D. Hilvert, J.
Am. Chem. Soc. 2018, 140, 1535–1543.
Acknowledgments
The authors are grateful to the Swiss National Science
Foundation and the ETH Zurich for generous support of this work.
We also thank Beat Blattmann and his team at the protein
crystallization facility at the University of Zurich for setting up
crystallization screens, the staff of the Swiss Light Source for
supporting x-ray data collection as well as Fabian Glatz for
assisting with SFC measurements. Plasmids pBK_PylRS,
[27] T. Hayashi, M. Tinzl, T. Mori, U. Krengel, J. Proppe, J. Soetbeer, D.
Klose, G. Jeschke, M. Reiher, D. Hilvert, Nat. Catal. 2018, 1, 578–584.
[28] H. Xiao, F. B. Peters, P. Yang, S. Reed, J. R. Chittuluru, P. G. Schultz,
ACS Chem. Biol. 2014, 9, 1092–1096.
pBAR_PylT_Barnase(2,44AMBER)
CAT(111AMBER)_T7RP(8,114AMBER)_GFP, were generously
provided by Jason Chin, MRC Laboratory of Molecular Biology.
and
pREP_PylT_
[29] T. S. Young, I. Ahmad, J. A. Yin, P. G. Schultz, J. Mol. Biol. 2010, 395,
361–374.
[30] J. D. Pédelacq, S. Cabantous, T. Tran, T. C. Terwilliger, G. S. Waldo,
Nat. Biotechnol. 2006, 24, 79–88.
Keywords: non-canonical ligands• genetic code expansion •
[31] E. J. Moore, R. Fasan, Tetrahedron 2019, 75, 2357–2363.
[32] S. W. Santoro, L. Wang, B. Herberich, D. S. King, P. G. Schultz, Nat.
Biotechnol. 2002, 20, 1044–1048.
myoglobin • heme protein catalysis • carbene transfer
[1]
[2]
T. L. Poulos, Chem. Rev. 2014, 114, 3919–3962.
O. F. Brandenberg, R. Fasan, F. H. Arnold, Curr. Opin. Biotechnol.
2017, 47, 102–111.
[33] V. Sharma, Y. S. Wang, W. R. Liu, ACS Chem. Biol. 2016, 11, 3305–
3309.
[34] J. Vojtěchovský, K. Chu, J. Berendzen, R. M. Sweet, I. Schlichting,
Biophys. J. 1999, 77, 2153–2174.
[3]
[4]
P. S. Coelho, E. M. Brustad, A. Kannan, F. H. Arnold, Science 2013,
339, 307–310.
[35] D. K. Garner, M. D. Vaughan, H. J. Hwang, M. G. Savelieff, S. M.
Berry, J. F. Honek, Y. Lu, J. Am. Chem. Soc. 2006, 128, 15608–15617.
[36] I. Efimov, G. Parkin, E. S. Millett, J. Glenday, C. K. Chan, H. Weedon,
H. Randhawa, J. Basran, E. L. Raven, FEBS Lett. 2014, 588, 701–704.
[37] P. Hosseinzadeh, Y. Lu, Biochim. Biophys. Acta 2016, 1857, 557–581.
[38] S. ichi Adachi, S. Nagano, Y. Watanabe, K. Ishimori, I. Morishima,
Biochem. Biophys. Res. Commun. 1991, 180, 138–144.
[39] S. C. Sun, B. C. Hsieh, M. C. Chuang, Electrochim. Acta 2019, 319,
766–774.
M. Bordeaux, V. Tyagi, R. Fasan, Angew. Chem. Int. Ed. 2015, 54,
1744–1748.
[5]
[6]
[7]
[8]
V. Tyagi, R. Fasan, Angew. Chem. Int. Ed. 2016, 55, 2512–2516.
V. Tyagi, R. B. Bonn, R. Fasan, Chem. Sci. 2015, 6, 2488–2494.
G. Sreenilayam, R. Fasan, Chem. Commun. 2015, 51, 1532–1534.
S. B. J. Kan, R. D. Lewis, K. Chen, F. H. Arnold, Science 2016, 354,
1048–1051.
[9]
X. Huang, M. Garcia-Borràs, K. Miao, S. B. J. Kan, A. Zutshi, K. N.
Houk, F. H. Arnold, ACS Cent. Sci. 2019, 5, 270–276.
[40] T. E. Carver, R. E. Brantley, E. W. Singleton, R. M. Arduini, M. L.
Quillin, G. N. Phillips, J. S. Olson, J. Biol. Chem. 1992, 267, 14443–
14450.
[10] S. B. J. Kan, X. Huang, Y. Gumulya, K. Chen, F. H. Arnold, Nature
2017, 552, 132–136.
[11] R. K. Zhang, X. Huang, F. H. Arnold, Curr. Opin. Chem. Biol. 2019, 49,
67–75.
[41] R. E. Brantley, S. J. Smerdon, A. J. Wilkinson, E. W. Singleton, J. S.
Olson, J. Biol. Chem. 1993, 268, 6995–7010.
[12] Y. B. Cai, S. Y. Yao, M. Hu, X. Liu, J. L. Zhang, Inorg. Chem. Front.
2016, 3, 1236–1244.
[42] Y. Wei, A. Tinoco, V. Steck, R. Fasan, Y. Zhang, J. Am. Chem. Soc.
2018, 140, 1649–1662.
[13] G. Sreenilayam, E. J. Moore, V. Steck, R. Fasan, Adv. Synth. Catal.
2017, 359, 2076–2089.
[43] D. A. Sharon, D. Mallick, B. Wang, S. Shaik, J. Am. Chem. Soc. 2016,
138, 9597–9610.
[14] K. Oohora, Y. Miyazaki, T. Hayashi, Angew. Chem. Int. Ed. 2019, 58,
13813–13817.
[44] K. Chen, S. Q. Zhang, O. F. Brandenberg, X. Hong, F. H. Arnold, J.
Am. Chem. Soc. 2018, 140, 16402–16407.
[15] H. M. Key, P. Dydio, D. S. Clark, J. F. Hartwig, Nature 2016, 534, 534–
537.
[16] P. Dydio, H. M. Key, A. Nazarenko, J. Y.-E. Rha, V. Seyedkazemi, D.
S. Clark, J. F. Hartwig, Science 2016, 354, 102–106.
[17] G. Sreenilayam, E. J. Moore, V. Steck, R. Fasan, ACS Catal. 2017, 7,
7629–7633.
5
This article is protected by copyright. All rights reserved.