综述与专题评论

基于非天然氨基酸的蛋白质合成研究进展

  • 赵梅 ,
  • 刘馨远 ,
  • 陈洋 ,
  • 商洁 ,
  • 丛宏日 ,
  • 马豪 ,
  • RAVIKUMAR Yuvaraj ,
  • 齐向辉
展开
  • (江苏大学 食品与生物工程学院,江苏 镇江,212013)
第一作者:博士,讲师(齐向辉教授为通信作者,E-mail:qxh@ujs.edu.cn)

收稿日期: 2023-07-11

  修回日期: 2023-08-08

  网络出版日期: 2024-07-11

基金资助

国家自然科学基金项目(32200061,32150410349);江苏省自然科学基金项目(BK20210752);中国博士后项目(2023T160278,2022M721390);科技部国家外专局项目(WGXZ2022038L)

Research progress on protein synthesis based on unnatural amino acids

  • ZHAO Mei ,
  • LIU Xinyuan ,
  • CHEN Yang ,
  • SHANG Jie ,
  • CONG Hongri ,
  • MA Hao ,
  • YUVARAJ RAVIKUMAR ,
  • QI Xianghui
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  • (School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China)

Received date: 2023-07-11

  Revised date: 2023-08-08

  Online published: 2024-07-11

摘要

蛋白质是生命体的重要组成部分,几乎参与了所有的生命活动。通常情况下生物体中蛋白质由20种天然氨基酸组成,但随着现代科技的飞速发展,人们对医疗、食品、材料等方面的需求日渐增大,这些蛋白质已经无法满足多样化的应用需求。随着非天然氨基酸及其合成的蛋白质的优异性能,使得利用非天然氨基酸改造蛋白质的技术逐渐成为研究热点。非天然氨基酸有着不同于天然氨基酸的侧链基团,可以给蛋白质带来新的性质与功能。该文基于对非天然氨基酸及非天然蛋白质的研究,首先介绍了以化学及生物的手段合成非天然氨基酸的方法,同时对化学及生物法的优劣势及未来的发展前景进行了总结;然后介绍了将非天然氨基酸掺入蛋白质的几种热门方法;接着对非天然氨基酸及其合成蛋白质的应用在酶的改造、科研以及医疗方面进行了列举和描述;最后对这项技术未来的发展进行了展望与总结。

本文引用格式

赵梅 , 刘馨远 , 陈洋 , 商洁 , 丛宏日 , 马豪 , RAVIKUMAR Yuvaraj , 齐向辉 . 基于非天然氨基酸的蛋白质合成研究进展[J]. 食品与发酵工业, 2024 , 50(12) : 336 -342 . DOI: 10.13995/j.cnki.11-1802/ts.036734

Abstract

Protein is an important component of living organisms and participates in almost all life activities.Under normal circumstances, the protein in the organism is composed of 20 natural amino acids.However, with the rapid development of modern science and technology, the demand for medical treatment, food, materials, and other aspects of people’s life is increasing, and these proteins can no longer meet the diversified application needs.At the same time, with the excellent performance of unnatural amino acids and their synthesized proteins are gradually becoming a research hot spot.The technology of modifying proteins with unnatural amino acids has been gradually developed.Unnatural amino acids have different side chain groups from natural amino acids, which can bring new properties and functions to proteins.Based on the study of unnatural amino acids and unnatural proteins, this review first introduces the chemical and biological methods for synthesizing unnatural amino acids, and summarizes the advantages and disadvantages of chemical and biological methods and their future development prospects.Then several popular methods of incorporating unnatural amino acids into proteins are presented.Then, the applications of unnatural amino acids and their synthetic proteins in enzyme modification, scientific research and medical treatment are listed and described.Finally, the future development of this technology is prospected and summarized.

参考文献

[1] ROS E, TORRES A G, RIBAS DE POUPLANA L.Learning from nature to expand the genetic code[J].Trends in Biotechnology, 2021, 39(5):460-473.
[2] JANG Y S, KIM B, SHIN J H, et al.Bio-based production of C2-C6 platform chemicals[J].Biotechnology and Bioengineering, 2012, 109(10):2437-2459.
[3] LIU C C, SCHULTZ P G.Adding new chemistries to the genetic code[J].Annual Review of Biochemistry, 2010, 79:413-444.
[4] BRUSTAD E M, ARNOLD F H.Optimizing non-natural protein function with directed evolution[J].Current Opinion in Chemical Biology, 2011, 15(2):201-210.
[5] WANG L.Expanding the genetic code[J].Science, 2003, 302(5645):584-585.
[6] 胡建强, 黄志平, 李晶.氨基酸手性拆分研究进展[J].食品与药品,2012, 14(1):60-64.
HU J Q, HUANG Z P, LI J.Research progress on chiral resolution of amino acids[J].Food and Drug,2012, 14(1):60-64.
[7] SHABICA A C, MAX T.Resolution of DL-tryptophan[J].Journal of the American Chemical Society,1949, 71(9):3251.
[8] 吴法浩. 非天然手性氨基酸合成的研究进展[J].生物化工,2020, 6(1):122-125;129.
WU F H.Advances in the synthesis of non-natural chiral amino acids[J].Biological Chemical Engineering,2020, 6(1):122-125;129.
[9] DANG T P, KAGAN H B.The asymmetric synthesis of hydratropic acid and amino-acids by homogeneous catalytic hydrogenation[J].Journal of the Chemical Society D:Chemical Communications,1971(10):481.
[10] IRIE K, ISHIDA A, NAKAMURA T, et al.Syntheses of substituted L- and D-tryptophans[J].Chemical and Pharmaceutical Bulletin,1984, 32(6):2126-2139.
[11] GIESE C, LEPTHIEN S, METZNER L, et al.Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells[J].ChemMedChem,2008, 3(9):1449-1456.
[12] 汤晓玲, 张慧敏, 柳志强, 等.非天然氨基酸细胞工厂的构建与应用[J].生物工程学报,2022, 38(4):1295-1306.
TANG X L, ZHANG H M, LIU Z Q, et al.Construction and application of microbial cell factories for unnatural amino acids[J].Chinese Journal of Biotechnology,2022, 38(4):1295-1306.
[13] ZHANG L L, CHEN J Z, CHEN N, et al.Cloning of two 5-aminolevulinic acid synthase isozymes HemA and HemO from Rhodopseudomonas palustris with favorable characteristics for 5-aminolevulinic acid production[J].Biotechnology Letters,2013, 35(5):763-768.
[14] KIND S, BECKER J, WITTMANN C.Increased lysine production by flux coupling of the tricarboxylic acid cycle and the lysine biosynthetic pathway—Metabolic engineering of the availability of succinyl-CoA in Corynebacterium glutamicum[J].Metabolic Engineering,2013, 15:184-195.
[15] MORA-VILLALOBOS J A, ZENG A P.Protein and pathway engineering for the biosynthesis of 5-hydroxytryptophan in Escherichia coli[J].Engineering in Life Sciences,2017, 17(8):892-899.
[16] MORA-VILLALOBOS J A, ZENG A P.Synthetic pathways and processes for effective production of 5-hydroxytryptophan and serotonin from glucose in Escherichia coli[J].Journal of Biological Engineering,2018, 12:3-15.
[17] DUGAR D, STEPHANOPOULOS G.Relative potential of biosynthetic pathways for biofuels and bio-based products[J].Nature Biotechnology,2011, 29(12):1074-1078.
[18] PIAO X Y, WANG L, LIN B X, et al.Metabolic engineering of Escherichia coli for production of L-aspartate and its derivative β-alanine with high stoichiometric yield[J].Metabolic Engineering,2019, 54:244-254.
[19] XU J M, LI J Q, ZHANG B, et al.Fermentative production of the unnatural amino acid l-2-aminobutyric acid based on metabolic engineering[J].Microbial Cell Factories,2019, 18(1):43.
[20] BRYANT K I, DILGER R N, PARSONS C M, et al.Dietary L-homoserine spares threonine in chicks 1,2[J].The Journal of Nutrition.2009, 139(7):1298-1302.
[21] OOGAI Y, YAMAGUCHI M, KAWADA-MATSUO M, et al.Lysine and threonine biosynthesis from aspartate contributes to Staphylococcus aureus growth in calf serum[J].Applied and Environmental Microbiology,2016, 82(20):6150-6157.
[22] 李珂. 有机溶剂/水两相中酶法合成非天然氨基酸以及甲苯降解菌的筛选、鉴定与降解特性研究[D].武汉:湖北大学,2018.
LI K.Study on the enzymatic synthesis of unnatural amino acids in organic solvent/water phases and screening, identification and degradation characteristics of toluene degrading bacteria[D].Wuhan:HuBei University,2018.
[23] 张春秋, 罗全, 刘俊秋, 等.蛋白质功能化新策略:嵌入非天然氨基酸[J].化学进展,2012, 24(4):577-588.
ZHANG C Q, LUO Q, LIU J Q, et al.New strategies for protein functionalization:Inserting unnatural amino acids into proteins[J].Progress in Chemistry,2012, 24(4):577-588.
[24] LIU J Q, JIANG M S, LUO G M, et al.Conversion of trypsin into a seleniumcontaining enzyme by using chemical mutation[J].Biotechnology Letters,1998, 20(7):693-696.
[25] KAISER E T, LAWRENCE D S.Chemical mutation of enzyme active sites[J].Science,1984, 226(4674):505-511.
[26] WANG Q, CHAN T R, HILGRAF R, et al.Bioconjugation by copper(I)-catalyzed azide-alkyne [3+2] cycloaddition[J].Journal of the American Chemical Society,2003, 125(11):3192-3193.
[27] 刘玉美, 毋彤, 陈振娅, 等.非天然氨基酸及非天然蛋白合成的研究进展[J].生物加工过程,2022, 20(2):182-194.
LIU Y M, WU T, CHEN Z Y, et al.Research progress in synthesis of unnatural amino acids and unnatural proteins[J].Chinese Journal of Bioprocess Engineering,2022, 20(2):182-194.
[28] KIMOTO M, HIRAO I.Genetic code engineering by natural and unnatural base pair systems for the site-specific incorporation of non-standard amino acids into proteins[J].Frontiers in Molecular Biosciences,2022, 9:851646.
[29] 杜方川, 王芬, 神应强, 等.非天然氨基酸修饰蛋白质研究进展[J].杭州师范大学学报(自然科学版),2013, 12(5):437-445.
DU F C, WANG F, SHEN Y Q, et al.Research progress of unnatural amino acid modified proteins[J].Journal of Hangzhou Normal University(Natural Science Edition),2013, 12(5):437-445.
[30] HANCOCK S M, UPRETY R, DEITERS A, et al.Expanding the genetic code of yeast for incorporation of diverse unnatural amino acids via a pyrrolysyl-tRNA synthetase/tRNA pair[J].Journal of the American Chemical Society,2010, 132(42):14819-14824.
[31] UGWUMBA I N, OZAWA K, XU Z Q, et al.Improving a natural enzyme activity through incorporation of unnatural amino acids[J].Journal of the American Chemical Society,2011, 133(2):326-333.
[32] BAKER P J, MONTCLARE J K.Enhanced refoldability and thermoactivity of fluorinated phosphotriesterase[J].Chembiochem,2011, 12(12):1845-1848.
[33] 史朝为, 石攀, 田长麟.非天然氨基酸在蛋白质动态特性核磁共振研究中的应用[J].波谱学杂志,2021,38(4):523-532.
SHI C W, SHI P, TIAN C L.Application of non-natural amino acids in the study of dynamic properties of proteins by NMR[J].Chinese Journal of Magnetic Resonance,2021,38(4):523-532.
[34] LIU Q, HE Q T, LYU X X, et al.DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe[J].Nature Communications,2020, 11(1):4857.
[35] 贺庆涛. GPCR调控arrestin构象多样性并指导其下游信号转导机制的研究. 济南: 山东大学, 2021.
HE Q T. Study on the mechanism of GPCR regulates the conformation diversity of arrestin and guides its downstream signal transduction. Jinan: Shandong University, 2021.
[36] MA J S.Unnatural amino acids in drug discovery[J].Chimica Oggi-Chemistry Today,2003, 21(6):65-68.
[37] LI Q K, CHEN Q, KLAUSER P C, et al.Developing covalent protein drugs via proximity-enabled reactive therapeutics[J].Cell,2020, 182(1):85-97.
[38] GRÜNEWALD J, HUNT G S, DONG L Q, et al.Mechanistic studies of the immunochemical termination of self-tolerance with unnatural amino acids[J].Proceedings of the National Academy of Sciences of the United States of America,2009, 106(11):4337-4342.
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