Donadio S, Staver M J, McAlpine J B, Swanson S J, Katz L
Corporate Molecular Biology Project, Abbott Laboratories, Abbott Park, IL 60064.
Gene. 1992 Jun 15;115(1-2):97-103. doi: 10.1016/0378-1119(92)90546-2.
The three eryA genes involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin in Saccharopolyspora erythraea, appear to be organized in a single transcriptional unit on the basis of the results of gene disruption experiments. An insertion sequence-like element of lower G + C content separates eryAI from eryAII. The organization of the enzymatic domains present in the eryA-encoded multifunctional polypeptides, determined by computer-assisted analysis, is presented. This has enabled the determination of a putative dehydratase domain. A rational approach for producing novel macrolides by introducing selected changes in polyketide synthase genes is outlined. The isolation of a lactone intermediate resulting from an early synthesis step in macrolactone formation is also presented.
参与糖多孢红霉菌中大环内酯类抗生素红霉素聚酮部分形成的三个eryA基因，根据基因破坏实验结果，似乎组织在一个单一的转录单元中。一个G + C含量较低的插入序列样元件将eryAI与eryAII分开。通过计算机辅助分析确定了eryA编码的多功能多肽中存在的酶结构域的组织方式。这使得能够确定一个推定的脱水酶结构域。概述了一种通过在聚酮合酶基因中引入选定的变化来生产新型大环内酯类化合物的合理方法。还介绍了在大环内酯形成早期合成步骤中产生的内酯中间体的分离。
