环二肽合酶生物合成途径研究进展  

Recent Advances in Cyclodipeptide Synthases-Dependent Biosynthetic Pathway

作　　者：张京星 姚婷婷[1] 刘晶 李花月 李文利[1,2] Zhang Jingxing;Yao Tingting;Liu Jing;Li Huayue;Li Wenli(Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003;Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237)

机构地区：[1]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 [2]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

出　　处：《有机化学》2019年第2期328-338,共11页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.31171201,81561148012,31570032)资助项目~~

摘　　要：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.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.

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 

分 类 号：TQ460.1[化学工程—制药化工]