• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

基因编码非天然氨基酸技术及其在生物医学领域的应用

朱银雪, 王德祥, 孔影, 陆文捷, 叶慧, 郝海平

朱银雪, 王德祥, 孔影, 陆文捷, 叶慧, 郝海平. 基因编码非天然氨基酸技术及其在生物医学领域的应用[J]. 中国药科大学学报, 2022, 53(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20220401
引用本文: 朱银雪, 王德祥, 孔影, 陆文捷, 叶慧, 郝海平. 基因编码非天然氨基酸技术及其在生物医学领域的应用[J]. 中国药科大学学报, 2022, 53(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20220401
ZHU Yinxue, WANG Dexiang, KONG Ying, LU Wenjie, YE Hui, HAO Haiping. Genetic incorporation of unnatural amino acids into proteins and its translational application in biomedicine[J]. Journal of China Pharmaceutical University, 2022, 53(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20220401
Citation: ZHU Yinxue, WANG Dexiang, KONG Ying, LU Wenjie, YE Hui, HAO Haiping. Genetic incorporation of unnatural amino acids into proteins and its translational application in biomedicine[J]. Journal of China Pharmaceutical University, 2022, 53(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20220401

基因编码非天然氨基酸技术及其在生物医学领域的应用

基金项目: 国家自然科学基金资助项目(No.82173783,No.81930109,No.81720108032);中央高校基本科研业务费资助项目(No.2632022YC03)

Genetic incorporation of unnatural amino acids into proteins and its translational application in biomedicine

Funds: This study was supported by the National Natural Science Foundation of China (No.82173783, No.81930109, No.81720108032) and the Fundamental Research Funds for the Central Universities (No.2632022YC03)
  • 摘要: 人体内蛋白质通常由20种天然氨基酸组成。氨基酸的不同排列组合及立体构象是构建丰富多样性的蛋白质的基础。近年来开发的突破性基因密码子拓展技术通过向目标蛋白质中定向引入非天然氨基酸,能够赋予原有的靶蛋白以共价结合邻近蛋白质、携带荧光基团、模拟蛋白质的翻译后修饰等新的生物学特性。本文从非天然氨基酸的结构和功能出发,介绍了不同类型的非天然氨基酸分别在调节蛋白质稳定性、研究蛋白质构象、表达水平、定位以及识别和增强蛋白质间亲和作用等方面的用途。此外,基因编码非天然氨基酸技术在生物医学领域的应用前景,将为生物药物的设计及优化提供全新的思路和方法。
    Abstract: Proteins in the human body are usually made of 20 natural amino acids.Through different amino acid combinations and isomerization, proteins of diverse functions are built.An emerging genetic code expansion technology can introduce unnatural amino acids into specific sites of target protein, endowing the protein with new biological characteristics including covalently binding with proximal proteins, carrying fluorescence, and mimicking specific protein post-translational modifications.In this paper, based on the structure and function of unnatural amino acids, the applications of different types of unnatural amino acids in regulating protein''s stability, studying protein''s conformation, expression level, and localization, and uncovering heretofore unknown protein-protein interactions were reviewed.Besides, genetic code expansion of unnatural amino acids is anticipated to find broad utilities in biomedicine by bringing new ideas and methods to the design and optimization of biologics.
  • [1] . Int J Mol Sci,2019,20(4):916.
    [2] Lv KM,Shao WY,Pedroso MM,et al. Enhancing the catalytic activity of a GH5 processive endoglucanase from Bacillus subtilis BS-5 by site-directed mutagenesis[J]. Int J Biol Macromol,2021,168:442-452.
    [3] Doering JA,Lee SH,Kristiansen K,et al. In silico site-directed mutagenesis informs species-specific predictions of chemical susceptibility derived from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool[J]. Toxicol Sci,2018,166(1):131-145.
    [4] Drienovská I,Roelfes G. Expanding the enzyme universe with genetically encoded unnatural amino acids[J]. Nat Catal,2020,3(3):193-202.
    [5] Dumas A,Lercher L,Spicer CD,et al. Designing logical codon reassignment - Expanding the chemistry in biology[J]. Chem Sci,2015,6(1):50-69.
    [6] Cao L,Wang L. New covalent bonding ability for proteins[J]. Protein Sci,2022,31(2):312-322.
    [7] Zambaldo C,Koh M,Nasertorabi F,et al. An orthogonal seryl-tRNA synthetase/tRNA pair for noncanonical amino acid mutagenesis in Escherichia coli[J]. Bioorg Med Chem,2020,28(20):115662.
    [8] Hu LM,Qin XW,Huang YJ,et al. Thermophilic pyrrolysyl-tRNA synthetase mutants for enhanced mammalian genetic code expansion[J]. ACS Synth Biol,2020,9(10):2723-2736.
    [9] Shao SD,Koh M,Schultz PG. Expanding the genetic code of the human hematopoietic system[J]. Proc Natl Acad Sci U S A,2020,117(16):8845-8849.
    [10] Nguyen TA,Cigler M,Lang K. Expanding the genetic code to study protein-protein interactions[J]. Angew Chem Int Ed Engl,2018,57(44):14350-14361.
    [11] Chung CZ,Amikura K,S?ll D. Using genetic code expansion for protein biochemical studies[J]. Front Bioeng Biotechnol,2020,8:1233.
    [12] Bedard PL,Hyman DM,Davids MS,et al. Small molecules,big impact: 20 years of targeted therapy in oncology[J]. Lancet,2020,395(10229):1078-1088.
    [13] Wang NX,Wang L. Genetically encoding latent bioreactive amino acids and the development of covalent protein drugs[J]. Curr Opin Chem Biol,2022,66:102106.
    [14] Zhu HQ,Tang XL,Zheng RC,et al. Recent advancements in enzyme engineering via site-specific incorporation of unnatural amino acids[J]. World J Microbiol Biotechnol,2021,37(12):213.
    [15] Smolskaya S,Andreev YA. Site-specific incorporation of unnatural amino acids into Escherichia coli recombinant protein: methodology development and recent achievement[J]. Biomolecules,2019,9(7):255.
    [16] Xiang Z,Ren HY,Hu YS,et al. Adding an unnatural covalent bond to proteins through proximity-enhanced bioreactivity[J]. Nat Methods,2013,10(9):885-888.
    [17] Coin I,Katritch V,Sun TT,et al. Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR[J]. Cell,2013,155(6):1258-1269.
    [18] Xiang Z,Lacey VK,Ren HY,et al. Proximity-enabled protein crosslinking through genetically encoding haloalkane unnatural amino acids[J]. Angew Chem Int Ed Engl,2014,53(8):2190-2193.
    [19] Yang B,Tang SB,Ma C,et al. Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions[J]. Nat Commun,2017,8(1):2240.
    [20] Furman JL,Kang MC,Choi S,et al. A genetically encoded aza-Michael acceptor for covalent cross-linking of protein-receptor complexes[J]. J Am Chem Soc,2014,136(23):8411-8417.
    [21] Xuan WM,Li J,Luo XZ,et al. Genetic incorporation of a reactive isothiocyanate group into proteins[J]. Angew Chem Int Ed Engl,2016,55(34):10065-10068.
    [22] Xuan WM,Shao SD,Schultz PG. Protein crosslinking by genetically encoded noncanonical amino acids with reactive aryl carbamate side chains[J]. Angew Chem Int Ed Engl,2017,56(18):5096-5100.
    [23] Wang NX,Yang B,Fu CY,et al. Genetically encoding fluorosulfate-L-tyrosine to react with lysine,histidine,and tyrosine via SuFEx in proteins in vivo[J]. J Am Chem Soc,2018,140(15):4995-4999.
    [24] Liu J,Cao L,Klauser PC,et al. A genetically encoded fluorosulfonyloxybenzoyl-L-lysine for expansive covalent bonding of proteins via SuFEx chemistry[J]. J Am Chem Soc,2021,143(27):10341-10351.
    [25] Li QK,Chen Q,Klauser PC,et al. Developing covalent protein drugs via proximity-enabled reactive therapeutics[J]. Cell,2020,182(1):85-97.e16.
    [26] Chin JW,Santoro SW,Martin AB,et al. Addition of p-azido-L-phenylalanine to the genetic code of Escherichia coli[J]. J Am Chem Soc,2002,124(31):9026-9027.
    [27] Chin JW,Martin AB,King DS,et al. Addition of a photocrosslinking amino acid to the genetic code of Escherichia coli[J]. Proc Natl Acad Sci USA,2002,99(17):11020-11024.
    [28] Hino N,Okazaki Y,Kobayashi T,et al. Protein photo-cross-linking in mammalian cells by site-specific incorporation of a photoreactive amino acid[J]. Nat Methods,2005,2(3):201-206.
    [29] Yanagisawa T,Hino N,Iraha F,et al. Wide-range protein photo-crosslinking achieved by a genetically encoded Nε-(benzyloxycarbonyl)lysine derivative with a diazirinyl moiety[J]. Mol Biosyst,2012,8(4):1131-1135.
    [30] Tian YL,Jacinto MP,Zeng Y,et al. Genetically encoded 2-aryl-5-carboxytetrazoles for site-selective protein photo-cross-linking[J]. J Am Chem Soc,2017,139(17):6078-6081.
    [31] Hu W,Yuan Y,Wang CH,et al. Genetically encoded residue-selective photo-crosslinker to capture protein-protein interactions in living cells[J]. Chem,2019,5(11):2955-2968.
    [32] Liu J,Li SS,Aslam NA,et al. Genetically encoding photocaged quinone methide to multitarget protein residues covalently in vivo[J]. J Am Chem Soc,2019,141(24):9458-9462.
    [33] Row RD,Nguyen SS,Ferreira AJ,et al. Chemically triggered crosslinking with bioorthogonal cyclopropenones[J]. ChemComm,2020,56(74):10883-10886.
    [34] Roy A,Barman S,Padhan J,et al. Engineering an acetyllysine reader with a photocrosslinking amino acid for interactome profiling[J]. ChemComm,2021,57(77):9866-9869.
    [35] Zhu XH,Akiyama T,Yokoyama T,et al. Stereoselective formation of β-O-4 structures mimicking softwood lignin biosynthesis:effects of solvent and the structures of quinone methide lignin models[J]. J Agric Food Chem,2019,67(25):6950-6961.
    [36] Ito S,Sugumaran M,Wakamatsu K. Chemical reactivities of ortho-quinones produced in living organisms: fate of quinonoid products formed by tyrosinase and phenoloxidase action on phenols and catechols[J]. Int J Mol Sci,2020,21(17):6080.
    [37] Liu J,Cheng RJ,Van Eps N,et al. Genetically encoded quinone methides enabling rapid,site-specific,and photocontrolled protein modification with amine reagents[J]. J Am Chem Soc,2020,142(40):17057-17068.
    [38] Chatterjee A,Guo JT,Lee HS,et al. A genetically encoded fluorescent probe in mammalian cells[J]. J Am Chem Soc,2013,135(34):12540-12543.
    [39] Charbon G,Brustad E,Scott KA,et al. Subcellular protein localization by using a genetically encoded fluorescent amino acid[J]. Chem Bio Chem,2011,12(12):1818-1821.
    [40] Jagadish K,Borra R,Lacey V,et al. Expression of fluorescent cyclotides using protein trans-splicing for easy monitoring of cyclotide-protein interactions[J]. Angew Chem Int Ed Engl,2013,52(11):3126-3131.
    [41] Alamudi SH,Satapathy R,Kim J,et al. Development of background-free tame fluorescent probes for intracellular live cell imaging[J]. Nat Commun,2016,7:11964.
    [42] Macek B,Forchhammer K,Hardouin J,et al. Protein post-translational modifications in bacteria[J]. Nat Rev Microbiol,2019,17(11):651-664.
    [43] Zhou JH,Zhao SW,Dunker AK. Intrinsically disordered proteins link alternative splicing and post-translational modifications to complex cell signaling and regulation[J]. J Mol Biol,2018,430(16):2342-2359.
    [44] Müller MM. Post-translational modifications of protein backbones: unique functions,mechanisms,and challenges[J]. Biochemistry,2018,57(2):177-185.
    [45] Hoppmann C,Wong A,Yang B,et al. Site-specific incorporation of phosphotyrosine using an expanded genetic code[J]. Nat Chem Biol,2017,13(8):842-844.
    [46] Venkat S,Nannapaneni DT,Gregory C,et al. Genetically encoding thioacetyl-lysine as a non-deacetylatable analog of lysine acetylation in Escherichia coli[J]. FEBS Open Bio,2017,7(11):1805-1814.
    [47] Luo XZ,Fu GS,Wang RE,et al. Genetically encoding phosphotyrosine and its nonhydrolyzable analog in bacteria[J]. Nat Chem Biol,2017,13(8):845-849.
    [48] Fottner M,Brunner AD,Bittl V,et al. Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase[J]. Nat Chem Biol,2019,15(3):276-284.
    [49] Beránek V,Reinkemeier CD,Zhang MS,et al. Genetically encoded protein phosphorylation in mammalian cells[J]. Cell Chem Biol,2018,25(9):1067-1074.e5.
    [50] Fu CY,Chen Q,Zheng F,et al. Genetically encoding a lipidated amino acid for extension of protein half-life in vivo[J]. Angew Chem Int Ed Engl,2019,58(5):1392-1396.
计量
  • 文章访问数:  983
  • HTML全文浏览量:  25
  • PDF下载量:  1032
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-03-11
  • 修回日期:  2022-05-31
  • 刊出日期:  2022-08-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭