中文摘要：

微生物能够产生众多结构和生物活性多样的次生代谢产物，而其生物合成基因簇的挖掘和异源表达是药物创新和产量提高的必要前提．在过去20年里，大量重要天然产物的生物合成基因簇在微生物中被不断的发现．在这些被挖掘的基因簇中，肽类抗生素的生物合成基因簇占了很大比重．肽类抗生素因具有抗茵、抗肿瘤、抗病毒等多种生物学活性而备受化学家和药物学家的重视．如能了解它们的生物合成机制，实现其基因簇的异源表达，将使合理化遗传修饰生物合成通路获取结构类似物（药物开发）和提高产量成为可能．大肠杆菌作为最广泛、最成功的表达体系，常用来表达外源基因，但一般只能表达一个或几个基因，却很少有用它来表达整个生物合成基因簇．2001年，Khosla和Cane在E．coli中成功异源表达了一个复杂聚酮天然产物（红霉素苷原6dEB）基因簇．这是首个有关在E．coli中异源表达天然产物生物合成基因簇的研究．至此之后，大肠杆菌开始作为生物合成基因簇的异源表达宿主，越来越受到相关领域的重视．紧接着核糖体肽和非核糖体肽生物合成基因簇也相继在大肠杆菌中成功异源表达．本文对肽类抗生素生物合成基因簇在E．coli中的异源表达进行了综述．

英文摘要：

Microorganisms produce a large number of secondary metabolites with amazing chemical diversities. Genome mining of their biosynthetic gene clusters and heterogeneous expression are essential for new drug discovery and yield improvement. In the past 20 years, numerous gene clusters responsible for the biosyntheses of important natural products have been identified. Among them, biosynthetic gene clusters for peptide antibiotics account for a large proportion. Peptide antibiotics have various biological activities including antibacterial, antitumor and antiviral activity, which have attracted considerable attention in chemical and pharmaceutical communities. Understanding of the biosynthetic mechanism and development of heterogeneous expression will pave the way for more rational structural modifications through combinant biosynthesis and yield improvements by metabolic engineering. E. coli, as the most extensive and successful expression system, is often employed to express exogenous genes. In general, E. coli is used to express one or several ~an,~ ~n,J r~,~l ,~ ~ ~ L_~ , ~cluster. Since the first exogenous biosynthesis gene cluster responsible for polyketide 6-deoxyerythronolide B （6dEB） was successfully expressed in E. coli in 2001 （Khosla and Cane）, E. coli as a heterogeneous host of gene cluster, has drawn high attention in the related fields. Then a number of ribosomal peptides and non-ribosomal peptides gene clusters have been successively expressed in E. Coli. This review summarizes the advances in the heterogeneous expression of biosynthetic gene clusters for assembly of peptide antibiotics in E. coli.