Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli
Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli
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DOI：
10.1038/nchembio803
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发表时间：
2006-08-01
影响因子：
14.8
通讯作者：
Oikawa, Hideaki
中科院分区：
文献类型：
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作者：
Watanabe, Kenji;Hotta, Kinya;Oikawa, Hideaki
非核糖体肽（NRP）是一类微生物次级代谢产物，其具有多种医学上重要的生物活性，例如抗生素（万古霉素）、免疫抑制（环孢菌素A）、抗病毒（卢佐肽A）和抗肿瘤（棘霉素和曲奥斯汀A）活性（1，2）。然而，许多微生物不适合培养，并且需要耗时的孵育条件的经验优化，以大量生产用于临床和商业用途的所需次级代谢产物（3）。因此，非常需要一种用于天然产物的异源生产的快速、简单的系统。在这里，我们展示了第一个例子的从头总生物合成的生物活性形式的异源NRP在大肠杆菌。我们的系统不仅可以作为一个有效的和灵活的平台，从简单的碳和氮源大规模制备天然产物，但也作为一个通用的工具，详细的表征和快速工程的生物合成途径的微生物合成的新化合物及其类似物。
Nonribosomal peptides (NRPs) are a class of microbial secondary metabolites that have a wide variety of medicinally important biological activities, such as antibiotic (vancomycin), immunosuppressive (cyclosporin A), antiviral (luzopeptin A) and antitumor (echinomycin and triostin A) activities(1,2). However, many microbes are not amenable to cultivation and require time-consuming empirical optimization of incubation conditions for mass production of desired secondary metabolites for clinical and commercial use(3). Therefore, a fast, simple system for heterologous production of natural products is much desired. Here we show the first example of the de novo total biosynthesis of biologically active forms of heterologous NRPs in Escherichia coli. Our system can serve not only as an effective and flexible platform for large-scale preparation of natural products from simple carbon and nitrogen sources, but also as a general tool for detailed characterizations and rapid engineering of biosynthetic pathways for microbial syntheses of novel compounds and their analogs.