环二肽合酶生物合成途径研究进展

doi:10.6023/cjoc201806003

有机化学 ›› 2019, Vol. 39 ›› Issue (2): 328-338.DOI: 10.6023/cjoc201806003 上一篇下一篇

综述与进展

环二肽合酶生物合成途径研究进展

张京星^a, 姚婷婷^a, 刘晶^a, 李花月^a,b, 李文利^a,b

a 中国海洋大学医药学院教育部海洋药物重点实验室青岛 266003;
b 青岛海洋科学与技术国家实验室海洋生物学与生物技术功能实验室青岛 266237

收稿日期:2018-06-01 修回日期:2018-09-10 发布日期:2018-09-18
通讯作者: 李文利 E-mail:liwenli@ouc.edu.cn
基金资助:
国家自然科学基金（Nos.31171201，81561148012，31570032）资助项目.

Recent Advances in Cyclodipeptide Synthases-Dependent Biosynthetic Pathway

Zhang Jingxing^a, Yao Tingting^a, Liu Jing^a, Li Huayue^a,b, Li Wenli^a,b

a Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003;
b Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237

Received:2018-06-01 Revised:2018-09-10 Published:2018-09-18
Contact: 10.6023/cjoc201806003 E-mail:liwenli@ouc.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 31171201, 81561148012, 31570032).

文章分享

摘要/Abstract

二酮哌嗪类化合物（DKPs）的特征结构是由两个α-氨基酸通过肽键缩合而成的环二肽（CDPs），稳定的六元环骨架结构使DKPs在药物化学中成为一个重要的药效团，表现出丰富的生物活性.合成可作为药物先导物的DKPs已日益引起人们的关注，其中，开展生物合成研究是拓宽其化学结构多样性的一个有效途径.与早期阐明的非核糖体肽合成酶（NRPSs）生物合成途径不同，环二肽合酶（CDPSs）以氨酰-tRNAs（aa-tRNAs）作为底物合成环二肽，其后修饰过程发生在环二肽形成之后.目前国内外已研究的经CDPS途径合成的二酮哌嗪类化合物报道了6例.对近年来环二肽合酶（CDPSs）生物合成途径相关研究进展进行了综述.

关键词: 二酮哌嗪类化合物, 非核糖体肽合成酶, 环二肽合酶, 生物合成途径

Diketopiperazines (DKPs) are derivatives of cyclodipeptides resulted from the condensation of two α-amino acids. The conformationally constrained six-membered ring makes DKP an attractive pharmacophore in medicinal chemistry, exhibiting a wide range of bioactivities. Recently, there has been increased interests in synthesizing DKPs and biosynthesis is an effective pathway to broaden their structural diversity. Different from non-ribosomal peptide synthetases (NRPSs)-dependent pathways, cyclodipeptide synthases (CDPSs) use aminoacyl-tRNAs (aa-tRNAs) as substrates and the resulting cyclodipeptides are further modified by associated tailoring enzymes to yield the final products. To date, six CDPS-dependent pathways for synthesizing DKPs compounds have been reported. A brief overview of recent progresses on CDPS-dependent DKPs biosynthetic pathway is provided.

Key words: diketopiperazines, non-ribosomal peptide synthetases, cyclodipeptide synthases, biosynthetic pathway

引用此文

张京星, 姚婷婷, 刘晶, 李花月, 李文利. 环二肽合酶生物合成途径研究进展[J]. 有机化学, 2019, 39(2): 328-338.

Zhang Jingxing, Yao Tingting, Liu Jing, Li Huayue, Li Wenli. Recent Advances in Cyclodipeptide Synthases-Dependent Biosynthetic Pathway[J]. Chin. J. Org. Chem., 2019, 39(2): 328-338.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[1] Borthwick, A. D. Chem. Rev. 2012, 112, 3641.
[2] Giessen, T. W.; Marahiel, M. A. Int. J. Mol. Sci. 2014, 15, 14610.
[3] Menegatti, S.; Hussain, M.; Naik, A. D. Biotechnol. Bioeng. 2013, 110, 857.
[4] de Carvalho, M. P.; Abraham, W. R. Curr. Med. Chem. 2012, 19, 3564.
[5] Kohna, H.; Widger, W. Curr. Drug Targets:Infect. Disord. 2005, 5, 273.
[6] Musetti, R.; Polizzotto, R.; Vecchione, A. Micron 2007, 38, 643.
[7] Ström, K.; Sjögren, J.; Broberg, A. Appl. Environ. Microbiol. 2002, 68, 4322.
[8] Rodriguez, P. L.; Carrasco, L. J. Virol. 1992, 66, 1971.
[9] Kanoh, K.; Kohno, S.; Katada, J. Bull. Agric. Chem. Soc. Jpn. 1999, 63, 1130.
[10] Kanzaki, H.; Yanagisawa, S.; Nitoda, T. Bull. Agric. Chem. Soc. Jpn. 2004, 68, 2341.
[11] Waring, P.; Beaver, J. Gen. Pharmacol. 1996, 27, 1311.
[12] Cornacchia, C.; Cacciatore, I.; Baldassarre, L. Mini-Rev. Med. Chem. 2012, 12, 2.
[13] Pérezpicaso, L.; Olivo, H. F.; Argotteramos, R. Bioorg. Med. Chem. Lett. 2012, 22, 7048.
[14] Bolognesi, M. L.; Ai, T. H.; Staderini, M. ChemMedChem 2010, 5, 1324.
[15] Song, M. K.; Hwang, I. K.; Rosenthal, M. J. Exp. Biol. Med. 2003, 228, 1338.
[16] Wang, G. X. Chin. J. Thromb. Hemostasis. 2011, 17, 234(in Chinese). (王贵鑫, 血栓与止血学, 2011, 17, 234.)
[17] Sun, T. W.; Ding, Z. P.; Wang, S. X. Chin. J. Mar. Drug. 2016, 4, 79(in Chinese). (孙天文, 丁忠鹏, 王世潇, 中国海洋药物, 2016, 4, 79.)
[18] Martins, M. B.; Carvalho, I. Tetrahedron 2007, 63, 9923.
[19] Zhang, H.; Ning, X.; Hang, H. Org. Lett. 2013, 15, 5670.
[20] Wen, L.; Liu, Q. Q.; Yang, Q. H. Prog. Mod. Biomed. 2012, 119, 2894.
[21] Rajesh Shinghal, M. D.; Allison Barnes, M. S.; Mahar, K. M. J. Sex. Med. 2013, 10, 2506.
[22] Charlton, P. A.; Faint, R. W.; Bent, F. Thromb. Haemostasis. 1996, 75, 808.
[23] Park, D. K.; Lee, K. E.; Baek, C. H. J. Bacteriol. 2006, 188, 2214.
[24] (a) Wyatt, P. G.; Allen, M. J.; Borthwick, A. D. Bioorg. Med. Chem. Lett. 2005, 15, 2579.
(b) Fischer, P. M. J. Pept. Sci. 2003, 9, 9.
(c) O'Neill, J. C.; Blackwell, H. E. Comb. Chem. High Throughput Screening. 2007, 10, 857.
(d) Merwe, E. V. D.; Huang, D.; Peterson, D.; Kilian, G.; Milne, P. J.; Venter, M. V. D. Peptides 2008, 29, 1305.
[25] Canu, N.; Belin, P.; Thai, R. Angew. Chem., Int. Ed. 2018, 57, 3118.
[26] Moutiez, M.; Seguin, J.; Fonvielle, M.; Belin, P.; Jacques, I. B.; Favry, E.; Arthur, M.; Gondry, M. Nucleic Acids Res. 2014, 42, 7247.
[27] Lautru, S.; Gondry, M.; Genet, R. Chem. Biol. 2002, 9, 1355.
[28] Moutiez, M.; Belin, P.; Gondry, M. Chem. Rev. 2017, 117, 5578.
[29] Li, W. L.; Xia, J. Microb. China 2014, 41, 111(in Chinese). (李文利, 夏娟, 微生物学通报, 2014, 41, 111.)
[30] Sauguet, L.; Moutiez, M.; Li, Y.; Belin, P.; Seguin, J.; Le Du, M.H.; Thai, R.; Masson, C.; Fonvielle, M.; Pernodet, J. L. Nucleic Acids Res. 2011, 39, 4475.
[31] Gondry, M.; Jacques, I. B.; Thai, R. Front. Microb. 2018, 9.
[32] Gondry, M.; Sauguet, L.; Belin, P. Nat. Chem. Biol. 2009, 5, 414.
[33] Jacques, I. B.; Moutiez, M.; Witwinowski, J. Nat. Chem. Biol. 2015, 11, 721.
[34] (a) Brockmeyer, K.; Li, S. M. J. Nat. Prod. 2017, 80, 2917.
(b) Mukai, T.; Reynolds, N. M.; Crnkovi?, A. Life 2017, 7, 8.
(c) Alqahtani, N.; Porwal, S. K.; James, E. D. Org. Biomol. Chem. 2015, 13, 7177.
(d) Sievers, F.; Wilm, A.; Dineen, D.; Gibson, T.J.; Karplus, K.; Li, W.; Lopez, R.; McWilliam, H.;Remmert, M.; Soding, J. Mol. Syst. Biol. 2011, 7, 539.
[35] (a) Bonnefond, L.; Arai, T.; Sakaguchi, Y. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 3912.
(b) Yaremchuk, A.; Kriklivyi, I.; Tukalo, M. EMBO J. 2002, 21, 3829.
(c) Jacques, I.; Seguin, J.; Moutiez, M. New Biotechnol. 2014, 31, S74.
(d) Cusack, S.; Berthet-Colominas, C.; Härtlein, M.; Nassar, N.; Leberman, R. Nature 1990, 347, 249.
[36] (a) Vetting, M. W.; Hegde, S. S.; Blanchard, J. S. Nat. Chem. Biol. 2010, 6, 797.
(b) Han, W.; Gao, J. F. Chem. Bioeng. 2013, 30, 17(in Chinese). (韩伟, 高菊芳, 化学与生物工程, 2013, 30, 17.)
[37] (a) Seguin, J.; Moutiez, M.; Li, Y. Chem. Biol. 2011, 18, 1362.
(b) Minelli, A.; Bellezza, I.; Grottelli, S.; Galli, F. Amino Acids 2008, 35, 283.
(c) Moutiez, M.; Schmitt, E.; Seguin, J. Nat. Commun. 2014, 5, 5141.
[38] Giessen, T. W.; von Tesmar, A. M.; Marahiel, M. A. Biochemistry 2013, 52, 4274.
[39] (a) Aravind, L.; De, S. R. F.; Iyer, L. M. Biol. Direct 2010, 5, 48.
(b) Belin, P.; Moutiez, M.; Lautru, S. Nat. Prod. Rep. 2012, 29, 961.
(c) Roback, P.; Beard, J.; Baumann, D. Nucleic Acids Res. 2007, 35, 5085.
[40] (a) Gondry, M.; Lautru, S.; Fusai, G. Eur. J. Biochem. 2001, 268, 1712.
(b) Belin, P.; Le Du, M.H.; Fielding, A.; Lequin, O.; Jacquet, M.; Charbonnier, J. B.; Lecoq, A.;Thai, R.; Courcon, M.; Masson, C. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 7426.
(c) Leys, D.; Mowat, C. G.; Mclean, K. J. J. Biol. Chem. 2003, 278, 5141.
(d) Seward, H. E.; Roujeinikova, A.; Mclean, K. J. J. Biol. Chem. 2006, 281, 39437.
[41] (a) Bourgeois, G.; Seguin, J.; Babin, M. J. Struct. Biol. 2018.
(b) Cryle, M. J.; Bell, S. G.; Schlichting, I. Biochemistry 2010, 49, 7282.
(c) Tang, M. R.; Sternberg, D.; Behr, R. K. Ind. Biotechnol. 2006, 2, 66.
[42] Zhang, Q.; Li, S.; Chen, Y.; Tian, X.; Zhang, H.; Zhang, G.; Zhu, Y.; Zhang, S.; Zhang, W.;Zhang, C. J. Antibiot. 2013, 66, 31.
[43] Skinnider, M. A.; Johnston, C. W.; Merwin, N. J. BMC Genomics. 2018, 19, 45.
[44] James, E. D.; Knuckley, B.; Alqahtani, N. ACS Synth. Biol. 2016, 5, 547.
[45] Johnson, J. A.; Lu, Y. Y.; Van Devente, J. A. Curr. Opin. Chem. Biol. 2010, 14, 774.
[46] Giessen, T. W.; Altegoer, F.; Nebel, A. J.; Steinbach, R. M.; Bange, G.; Marahiel, M. A. Angew. Chem., Int. Ed. 2015, 54, 2492.
[47] Giessen, T. W.; Marahiel, M. A. Front. Microb. 2015, 6, 785.
[48] McLean, K. J.; Cheesman, M.R.; Rivers, S.L.; Richmond, A.; Leys, D.; Chapman, S. K.; Reid, G. A.; Price, N. C.; Kelly, S. M.; Clarkson, J.; Smith, W. E.; Munro, A. W. J. Inorg. Biochem. 2002, 91, 527.
[49] Bonnefond, L.; Arai, T.; Sakaguchi, Y. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 3912.
[50] Liu, J.; Yu, H.; Li, S. M. Appl. Microbiol. Biotechnol. 2018, 102, 4435.
[51] Yao, T. T.; Liu, J.; Liu, Z. Z.; Li, T.; Li, H. Y.; Che, Q.; Zhu, T. J.; Li, D. H.; Gu, Q. Q.; Li, W. L. Nat. Commun. 2018, 9, 4091.
[52] (a) Li, S. M. ChemInform 2010, 27, 57.
(b) Xu, W.; Gavia, D. J.; Tang, Y. Nat. Prod. Rep. 2014, 31, 1474.
(c) Alkhalaf, L. M.; Ryan, K. S. Chem. Biol. 2015, 22, 317.
(d) Walsh, C. T. ACS Chem. Biol. 2014, 9, 2718.
[53] Fan, A.; Winkelblech, J.; Li, S. M. Appl. Microbiol. Biotechnol. 2015, 99, 7399.
[54] (a) Meng, S.; Han, W.; Zhao, J.; Jian, X. H.; Pan, H. X.; Tang, G. L. Angew. Chem., Int. Ed. 2018, 57, 719.
(b) Patteson, J.; Cai, W.; Johnson, R. A.; Santa, M. K.; Li, B. Biochemistry 2017, 57, 61.
[55] Kohn, H.; Widger, W. Curr. Drug Targets:Infect. Disord. 2005, 5, 273.
[56] Schmitt, E.; Bourgeois, G.; Gondry, M.; Aleksandrov, A. Sci. Rep. 2018, 8, 7031.
[57] Wunsch, C.; Mundt, K.; Li, S. M. Appl. Microbiol. Biotechnol. 2015, 99, 4213.
[58] Vior, N. M.; Lacret, R.; Chandra, G.; Dorairaj, S.; Trick, M. & Truman, A. W. Appl. Environ. Microbiol. 2018, 84(9), UNSP/e02828-17.
[59] Prasad, C. Peptides 1995, 16, 151.
[60] Giessen, T. W.; von Tesmar, A. M.; Marahiel, M. A. Chem. Biol. 2013, 20, 828.

环二肽合酶生物合成途径研究进展

Recent Advances in Cyclodipeptide Synthases-Dependent Biosynthetic Pathway

PDF

可视化

摘要/Abstract

引用此文

分享此文

参考文献

相关文章 4

编辑推荐

相关统计

本文评价

[1]	吴世文, 杨盟权, 肖友利. 单萜吲哚生物碱的合成生物学研究进展[J]. 有机化学, 2018, 38(9): 2243-2258.
[2]	王平平, 杨成帅, 李晓东, 蒋雨果, 严兴, 周志华. 植物天然化合物的人工合成之路[J]. 有机化学, 2018, 38(9): 2199-2214.
[3]	陈单丹, 岑沛霖, 刘文, 徐志南. 大环内酯类免疫抑制剂他克莫司的生物合成机制研究进展[J]. 有机化学, 2013, 33(06): 1254-1262.
[4]	唐满成, 唐功利. 抗肿瘤活性四氢异喹啉类抗生素的生物合成研究进展[J]. 有机化学, 2012, 32(9): 1568-1576.