Hopwood D A, Malpartida F, Kieser H M, Ikeda H, Duncan J, Fujii I, Rudd B A, Floss H G, Omura S
Nature. 1985;314(6012):642-4. doi: 10.1038/314642a0.
The recent development of molecular cloning systems in Streptomyces has made possible the isolation of biosynthetic genes for some of the many antibiotics produced by members of this important genus of bacteria. Such clones can now be used to test the idea that novel antibiotics could arise through the transfer of biosynthetic genes between streptomycetes producing different antibiotics. The likelihood of a 'hybrid' compound being produced must depend on the substrate specificities of the biosynthetic enzymes, about which little is known. In attempts to demonstrate hybrid antibiotic production, we therefore began with strains producing different members of the same chemical class of compounds in order to maximize the chance of success. Here we report the production of novel compounds by gene transfer between strains producing the isochromanequinone antibiotics actinorhodin, granaticin and medermycin. These experiments were made possible by the recent cloning of the whole set of genes for the biosynthetic pathway of actinorhodin from Streptomyces coelicolor A3(2) (ref. 8). We believe that this represents the first report of the production of hybrid antibiotics by genetic engineering.
链霉菌分子克隆系统的最新进展使得分离该重要细菌属成员所产生的众多抗生素中某些抗生素的生物合成基因成为可能。现在，此类克隆可用于检验这样一种观点，即新型抗生素可能通过产生不同抗生素的链霉菌之间生物合成基因的转移而产生。产生“杂交”化合物的可能性必定取决于生物合成酶的底物特异性，而对此了解甚少。因此，为了最大程度地提高成功几率，在尝试证明杂交抗生素的产生时，我们从产生同一化学类别化合物不同成员的菌株入手。在此，我们报告了通过在产生异色满醌抗生素放线紫红素、granaticin和medermycin的菌株之间进行基因转移而产生新型化合物的情况。最近从天蓝色链霉菌A3(2)克隆了放线紫红素生物合成途径的全套基因（参考文献8），才使得这些实验得以进行。我们认为，这代表了通过基因工程生产杂交抗生素的首次报道。
