金属酶在生物体中发挥着多种至关重要的作用，而人工金属酶的分子设计能够调控和拓展天然金属酶的功能，甚至创造出功能更为优越的新型酶分子。肌红蛋白（Mb）是作为血红素蛋白或其他金属蛋白分子设计的理想蛋白模型。近些年，基于Mb蛋白骨架的人工金属酶的分子设计逐渐发展了多种研究策略，包括设计氢键网络、金属结合位点、分子内二硫键、利用蛋白翻译后修饰、引入非天然氨基酸和非天然辅基等。本文着重综述这些方面的最新研究进展，可以帮助我们深刻认识金属酶的结构与功能关系，同时掌握人工金属酶分子设计的思路与方法，从而有助于推动这一领域的快速发展。
Metalloenzymes play diverse important functions in biological systems. Meanwhile, design of artificial metalloenzymes may fine-tune and expand the functionalities of natural metalloenzymes, and even create novel enzymes with more advanced functions. Myoglobin(Mb) is an ideal protein model for design of heme proteins and other metalloenzymes. In recent years, various approaches have been developed for design of artificial metalloenzymes based on the protein scaffold of Mb, which include design of hydrogen-bonding network, intramolecular disulfide bond, the use of post-translational modifications, introduction of non-natural amino acids and non-native cofactors. This review summaries the recent progress in these aspects, which will help us understand the structure and function relationship of metalloenzymes, master the idea and methodologies of artificial metalloenzyme design, thereby promoting the rapid development in this field.
Contents
1 Introduction
2 Approaches and cases studies
2.1 Design of hydrogen-bonding network
2.2 Design of metal-binding site
2.3 Design of disulfide bond
2.4 Use of post-translational modifications
2.5 Introduction of non-natural amino acids
2.6 Introduction of non-native cofactors
3 Conclusion and outlook
[1] Poulos T L. Chem. Rev., 2014, 114:3919.
[2] Liu J, Chakraborty S, Hosseinzadeh P, Yu Y, Tian S, Petrik I, Bhagi A, Lu Y. Chem. Rev., 2014, 114:4366.
[3] Huang X, Groves J T. Chem. Rev., 2018, 118:2491.
[4] Waldron K J, Rutherford J C, Ford D, Robinson N J. Nature, 2009, 460:823.
[5] Valdez C E, Smith Q A, Nechay M R, Alexandrova A N. Acc. Chem. Res., 2014, 47:3110.
[6] Lu Y, Berry S M, Pfister T D. Chem. Rev., 2001, 101:3047.
[7] Lu Y, Yeung N, Sieracki N, Marshall N M. Nature, 2009, 460:855.
[8] Lin Y W, Sawyer E B, Wang J Y. Chem. Asian J., 2013, 8:2534.
[9] Petrik I D, Liu J, Lu Y. Curr. Opin. Chem. Biol., 2014, 19:67.
[10] Huang P S, Boyken S E, Baker D. Nature, 2016, 537:320.
[11] Nastri F, Chino M, Maglio O, Bhagi-Damodaran A, Lu Y, Lombardi A. Chem. Soc. Rev., 2016, 45:5020.
[12] Lin Y W. Coord. Chem. Rev., 2017, 336:1.
[13] Hu C, Yu Y, Wang J Y. Chem. Commun. (Camb.)., 2017, 53:4173.
[14] Schwizer F, Okamoto Y, Heinisch T, Gu Y, Pellizzoni M M, Lebrun V, Reuter R, Kohler V, Lewis J C, Ward T R. Chem. Rev., 2018, 118:142.
[15] Moody P C E, Raven E L. Acc. Chem. Res., 2018, 51:427.
[16] Hirota S, Lin Y W. J. Biol. Inorg. Chem., 2018, 23:7.
[17] Lin Y, Wang J Y, Lu Y. Sci. China Chem., 2014, 57:346.
[18] Du J F, Li W, Li L, Wen G B, Lin Y W, Tan X. ChemistryOpen, 2015, 4:97.
[19] Zeng J, Zhao Y, Li W, Tan X, Wen G B, Lin Y W. J. Mol. Catal. B:Enzym., 2015, 111:9.
[20] Zhao Y, Du K J, Gao S Q, He B, Wen G B, Tan X, Lin Y W. J. Inorg. Biochem., 2016, 156:113.
[21] Wu L B, Yuan H, Gao S Q, You Y, Nie C M, Wen G B, Lin Y W, Tan X. Nitric Oxide, 2016, 57:21.
[22] Wu L B, Du K J, Nie C M, Gao S Q, Wen G B, Tan X, Lin Y W. J. Mol. Catal. B:Enzym., 2016, 134:367.
[23] Ferguson-Miller S, Babcock G T. Chem. Rev., 1996, 96:2889.
[24] Sigman J A, Kwok B C, Lu Y. J. Am. Chem. Soc., 2000, 122:8192.
[25] Miner K D, Mukherjee A, Gao Y G, Null E L, Petrik I D, Zhao X, Yeung N, Robinson H, Lu Y. Angew. Chem. Int. Ed., 2012, 51:5589.
[26] Petrik I D, Davydov R, Ross M, Zhao X, Hoffman B, Lu Y. J. Am. Chem. Soc., 2016, 138:1134.
[27] Buschmann S, Warkentin E, Xie H, Langer J D, Ermler U, Michel H. Science, 2010, 329:327.
[28] Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S. Science, 1996, 272:1136.
[29] Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, Murata T, Iwata S, Shiro Y. Science, 2010, 330:1666.
[30] Sundaramoorthy M, Kishi K, Gold M H, Poulos T L. J. Mol. Biol., 1994, 238:845.
[31] Sigman J A, Kim H K, Zhao X, Carey J R, Lu Y. Proc. Natl. Acad. Sci. U. S. A., 2003, 100:3629.
[32] Yeung N, Lin Y W, Gao Y G, Zhao X, Russell B S, Lei L, Miner K D, Robinson H, Lu Y. Nature, 2009, 462:1079.
[33] Bhagi-Damodaran A, Michael M A, Zhu Q, Reed J, Sandoval B A, Mirts E N, Chakraborty S, Moënne-Loccoz P, Zhang Y, Lu Y. Nat. Chem., 2017, 9:257.
[34] Lin Y W, Yeung N, Gao Y G, Miner K D, Tian S, Robinson H, Lu Y. Proc. Natl. Acad. Sci. U. S. A., 2010, 107:8581.
[35] Matsumura H, Hayashi T, Chakraborty S, Lu Y, Moënne-Loccoz P. J. Am. Chem. Soc., 2014, 136:2420.
[36] Matsumura H, Chakraborty S, Reed J, Lu Y, Moënne-Loccoz P. Biochemistry, 2016, 55:2091.
[37] Lin Y W. Inorg. Chem. Front., 2017, 4:918.
[38] Reed J H, Shi Y, Zhu Q, Chakraborty S, Mirts E N, Petrik I D, Bhagi-Damodaran A, Ross M, Moënne-Loccoz P, Zhang Y, Lu Y. J. Am. Chem. Soc., 2017, 139:12209.
[39] Sun M H, Li W, Liu J H, Wen G B, Tan X, Lin Y W. RSC Adv., 2013, 3:9337.
[40] Castello P R, David P S, McClure T, Crook Z, Poyton R O. Cell metabol., 2006, 3:277.
[41] Bhagi-Damodaran A, Reed J H, Zhu Q, Shi Y, Hosseinzadeh P, Sandoval B A, Harnden K A, Wang S, Sponholtz M R, Mirts E N, Dwaraknath S, Zhang Y, Moënne-Loccoz P, Lu Y. Proc. Natl. Acad. Sci. U. S. A., 2018, 115:6195.
[42] Suzuki S, Kataoka K, Yamaguchi K. Acc. Chem. Res., 2000, 33:728.
[43] Shu X G, Su J H, Du K J, You Y, Gao S Q, Wen G B, Tan X, Lin Y W. ChemistryOpen, 2016, 5:192.
[44] Hagihara Y, Saerens D. Biochim. Biophys. Acta, 2014, 1844:2016.
[45] Tiso M, Tejero J, Basu S, Azarov I, Wang X, Simplaceanu V, Frizzell S, Jayaraman T, Geary L, Shapiro C, Ho C, Shiva S, Kim-Shapiro D B, Gladwin M T. J. Biol. Chem., 2011, 286:18277.
[46] Guimaraes B G, Hamdane D, Lechauve C, Marden M C, Golinelli-Pimpaneau B. Acta Crystallogr. D Biol. Crystallogr., 2014, 70:1005.
[47] Ascenzi P, Di Masi A, Leboffe L, Fiocchetti M, Nuzzo M T, Brunori M, Marino M. Mol. Aspects Med., 2016, 52:1.
[48] Ascenzi P, Marino M, Polticelli F, Coletta M, Gioia M, Marini S, Pesce A, Nardini M, Bolognesi M, Reeder B J, Wilson M T. Biochim. Biophys. Acta, 2013, 1834:1750.
[49] Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y. J. Mol. Biol., 2004, 339:873.
[50] Astudillo L, Bernad S, Derrien V, Sebban P, Miksovska J. J. Inorg. Biochem., 2013, 129:23.
[51] Beckerson P, Reeder B J, Wilson M T. FEBS Lett., 2015, 589:507.
[52] Boron I, Capece L, Pennacchietti F, Wetzler D E, Bruno S, Abbruzzetti S, Chisari L, Luque F J, Viappiani C, Marti M A, Estrin D A, Nadra A D. Biochim. Biophys. Acta, 2015, 1850:169.
[53] Wu L B, Yuan H, Zhou H, Gao S Q, Nie C M, Tan X, Wen G B, Lin Y W. Arch. Biochem. Biophys., 2016, 600:47.
[54] Yin L L, Yuan H, Du K J, He B, Gao S Q, Wen G B, Tan X, Lin Y W. Chem. Commun. (Camb.)., 2018, 54:4356.
[55] Zhao J, Lu C, Franzen S. J. Phys. Chem. B, 2015, 119:12828.
[56] Lin Y W. Arch. Biochem. Biophys., 2018, 641:1.
[57] Lin Y W. Biochim. Biophys. Acta, 2015, 1854:844.
[58] Barker P D, Ferrer J C, Mylrajan M, Loehr T M, Feng R, Konishi Y, Funk W D, MacGillivray R T, Mauk A G. Proc. Natl. Acad. Sci. U.S.A., 1993, 90:6542.
[59] Lin Y W, Wang W H, Zhang Q, Lu H J, Yang P Y, Xie Y, Huang Z X, Wu H M. ChemBioChem, 2005, 6:1356.
[60] Hu S, He B, Du K J, Wang X J, Gao S Q, Lin Y W. ChemistryOpen, 2017, 6:325.
[61] Cheng H M, Yuan H, Wang X J, Xu J K, Gao S Q, Wen G B, Tan X, Lin Y W. J. Inorg. Biochem., 2018, 182:141.
[62] Yan D J, Li W, Xiang Y, Wen G B, Lin Y W, Tan X. ChemBioChem, 2015, 16:47.
[63] Yan D J, Yuan H, Li W, Xiang Y, He B, Nie C M, Wen G B, Lin Y W, Tan X. Dalton Trans., 2015, 44:18815.
[64] Li L L, Yuan H, Liao F, He B, Gao S Q, Wen G B, Tan X, Lin Y W. Dalton Trans., 2017, 46:11230.
[65] Lu Y. Curr. Opin. Chem. Biol., 2005, 9:118.
[66] Lewis J C. Curr. Opin. Chem. Biol., 2015, 25:27.
[67] Yu Y, Hu C, Xia L, Wang J Y. ACS Catal., 2018, 8:1851.
[68] Liu X, Yu Y, Hu C, Zhang W, Lu Y, Wang J Y. Angew. Chem. Int. Ed., 2012, 124:4388.
[69] Yu Y, Zhou Q, Wang L, Liu X, Zhang W, Hu M, Dong J, Li J, Lv X, Ouyang H, Li H, Gao F, Gong W, Lu Y, Wang J Y. Chem. Sci., 2015, 6:3881.
[70] Zhou Q, Hu M, Zhang W, Jiang L, Perrett S, Zhou J, Wang J Y. Angew. Chem. Int. Ed., 2013, 52:1203.
[71] Chand S, Ray S, Wanigasekara E, Yadav P, Crawford J A, Armstrong D W, Rajeshwar K, Pierce B S. Arch. Biochem. Biophys., 2018, 639:44.
[72] Ensign A A, Jo I, Yildirim I, Krauss T D, Bren K L. Proc. Natl. Acad. Sci. U. S. A., 2008, 105:10779.
[73] Heinecke J L, Yi J, Pereira J C, Richter-Addo G B, Ford P C. J. Inorg. Biochem., 2012, 107:47.
[74] Posey J E, Gherardini F C. Science, 2000, 288:1651.
[75] Sommer D J, Vaughn M D, Ghirlanda G. Chem. Commun. (Camb.), 2014, 50:15852.
[76] Key H M, Dydio P, Clark D S, Hartwig J F. Nature, 2016, 534:534.
[77] Sreenilayam G, Moore E J, Steck V, Fasan R. Adv. Synth. Catal., 2017, 359:2076.
[78] Cai Y B, Li X H, Jing J, Zhang J L. Metallomics, 2013, 5:828.
[79] 蔡元博(Cai Y B), 张俊龙(Zhang J L).中国科学:化学(Scientia Sinica Chimica), 2014, 44:555.
[80] Cai Y B, Yao S Y, Hu M, Liu X, Zhang J L. Inorg. Chem. Front., 2016, 3:1236.
[81] Shi Z H, Du K J, He B, Gao S Q, Wen G B, Lin Y W. Inorg. Chem.Front., 2017, 4:2033.
[82] Ozaki S I, Matsui T, Roach M P, Watanabe Y. Coord. Chem. Rev., 2000, 198:39.
[83] Ueno T, Abe S, Yokoi N, Watanabe Y. Coord. Chem. Rev., 2007, 251:2717.
[84] Hayashi T, Sano Y, Onoda A. Isr. J. Chem., 2015, 55:76.
[85] Carey J R, Ma S K, Pfister T D, Garner D K, Kim H K, Abramite J A, Wang Z, Guo Z, Lu Y. J. Am. Chem. Soc., 2004, 126:10812.
[86] Garner D K, Liang L, Barrios D A, Zhang J L, Lu Y. ACS Catal., 2011, 1:1083.
[87] Zhang J L, Garner D K, Liang L, Chen Q, Lu Y. Chem. Commun. (Camb.), 2008, 1665.
[88] Zhang J L, Garner D K, Liang L, Barrios D A, Lu Y. Chem. Eur. J., 2009, 15:7481.
[89] Hayashi T, Morita Y, Mizohata E, Oohora K, Ohbayashi J, Inoue T, Hisaeda Y. Chem. Commun. (Camb.), 2014, 50:12560.
[90] Morita Y, Oohora K, Sawada A, Doitomi K, Ohbayashi J, Kamachi T, Yoshizawa K, Hisaeda Y, Hayashi T. Dalton Trans., 2016, 45:3277.
[91] Oohora K, Meichin H, Kihira Y, Sugimoto H, Shiro Y, Hayashi T. J. Am. Chem. Soc., 2017, 139:18460.
[92] Oohora K, Meichin H, Zhao L, Wolf M W, Nakayama A, Hasegawa J Y, Lehnert N, Hayashi T. J. Am. Chem. Soc., 2017, 139:17265.
[93] Sreenilayam G, Moore E J, Steck V, Fasan R. ACS Catal., 2017, 7:7629.
[94] Lin Y W, Nagao S, Zhang M, Shomura Y, Higuchi Y, Hirota S. Angew. Chem. Int. Ed., 2015, 54:511.
[95] Nanda V, Koder R L. Nat. Chem., 2010, 2:15.
[96] Kries H, Blomberg R, Hilvert D. Curr. Opin. Chem. Biol., 2013, 17:221.
[97] Lin Y W, Nie C M, Liao L F. J. Mol. Model., 2012, 18:4409.
[98] Zhang M, Nakanishi T, Yamanaka M, Nagao S, Yanagisawa S, Shomura Y, Shibata N, Ogura T, Higuchi Y, Hirota S. ChemBioChem, 2017, 18:1712.
[99] Lin Y W. Proteins, 2011, 79:679.
[100] Marshall N M, Garner D K, Wilson T D, Gao Y G, Robinson H, Nilges M J, Lu Y. Nature, 2009, 462:113.
[101] Heinisch T, Ward T R. Acc. Chem. Res., 2016, 49:1711.
[102] Peacock A F. Curr. Opin. Chem. Biol., 2013, 17:934.
[103] Woolfson D N, Bartlett G J, Burton A J, Heal J W, Niitsu A, Thomson A R, Wood C W. Curr. Opin. Struct. Biol., 2015, 33:16.
[104] Boyken S E, Chen Z, Groves B, Langan R A, Oberdorfer G, Ford A, Gilmore J M, Xu C, DiMaio F, Pereira J H, Sankaran B, Seelig G, Zwart P H, Baker D. Science, 2016, 352:680.
[105] Yin L L, Yuan H, Liu C, He B, Gao S Q, Wen G B, Tan X, Lin Y W. ACS Catal., 2018, 8:9619.
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