醌霉素类抗生素生物合成研究进展  

Advance in the Research on Quinomycins Biosynthesis

作　　者：张晨[1] 孔令新[1] 雷璇[1] 邓子新[1] 由德林[1] 

机构地区：[1]上海交通大学生命科学技术学院微生物代谢国家重点实验室,上海200030

出　　处：《有机化学》2014年第6期1240-1252,共13页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.31170085;31070058);国家重点基础研究发展计划(No.2012CB721004)资助项目~~

摘　　要：醌霉素是一类由链霉菌产生的环状寡肽抗生素,结构上拥有一对特征性喹喔啉-2-甲酰基或3-羟基喹啉-2-甲酰基单元.醌霉素选择性插入到DNA分子的碱基对之间,抑制DNA的复制和转录,因而具有良好的肿瘤抑制活性.综述了近十年来醌霉素家族抗生素的生物合成研究进展,通过比较醌霉素不同代表成员的基因簇,归纳这些化合物与其它类型天然产物生物合成以及色氨酸分解代谢中的相似反应,并剖析催化这些反应的酶的功能特性,揭示了醌霉素的化学结构特征和其不同成员之间结构差异的形成原因.在此基础上,还介绍了在异源宿主大肠杆菌中用组合生物合成的方法产生醌霉素类非天然的天然产物的范例,展示了该类抗生素工业化生产的潜力.Quinomycins are a type of cyclic oligopeptide antibiotics, featuring a pair of moieties, either quinoxaline-2-carboxy or 3-hydroxyquinoline-2-carboxy group. The characteristic structural units are capable of intercalating preferentially into particular DNA basepairs, thereby inhibiting DNA replication and transcription and hence confer remarkable tumor-inhibiting potency to quinomycins. Herein, an overview is made about the development of the exploration on quinomycin biosynthesis mainly during the past decade. Biosynthetic gene clusters are compared among various quinomycin family members, common biochemical reactions experienced in the biosynthesis of these compounds and natural products of other types as well as tryptophan catabolism are inducted with functional characteristics of the enzymes responsible for these reactions dissected, concurrently lending profundity to the revelation of the reasons for the formation of structural features shared and variances differentiated by quinomycins. Based on the elaboration, an exemplar is presented about the combinatorial biosynthesis in E. coli, the heterologous host to produce the unnatural natural product of quinomycin family, showing the potentiality of industrialization for the biosynthesis.

关 键 词：肿瘤抑制 醌霉素 天然产物 生物合成 

分 类 号：TQ465[化学工程—制药化工]