基因工程改造生物合成肽类抗生素

Gene Engineered Biosynthesis of Peptide Antibiotics

许多微生物是以非核糖体方式合成生物活性肽。生物活性肽的合成以及它们的序列专一性是由一定数目按顺序排列的蛋白质模板所决定的。因此可以构建一种编码肽合成酶系的杂交基因,从而改变肽合成酶系对底物专一性。这里介绍一种两步重组法(two-stepmethod)在基因水平取代相应的蛋白质模板中的一个氨基酸激活功能域。这种技术显示了将基因工程方法用于肽类抗生素生物合成的潜力。

A wide variety of bioactive peptides are produced nonribosomally in microbes. It has now been established that the synthesis of bioactive peptides and the specifications of their sequence are brought about by a protein template that contains the appropriate number and the correct order of activating units. These advances enable the development of a technique that permits the construction of hybrid genes encoding the peptides antibiotics. It utilizes successive gene disruption and reconstitution and demonstrates, for the first time, the potential of genetic engineering in the biosynthesis and of novel peptide antibiotics.