GENETIC DESIGNS FOR HIGH-EFFICIENCY MACROLIDE PRODUCTION

大环内酯类抗生素是微生物天然产物，在临床上有着广泛的应用 和兽医学。红霉素是研究得最好的例子， 大环内酯类抗生素;雷帕霉素和FK 506是有希望的新的 免疫抑制剂大环内酯类。大环内酯类的价格和可用性 取决于它们的生产效率，因此，取决于它们的遗传学。 生产菌株。最近，大学研究表明， 抗生素调控基因的拷贝数急剧增加 提高了模型抗生素化合物的生产水平。 FermaLogic的科学家们熟悉执行所需的工具， 在大环内酯生产生物体中的类似实验。在第一阶段，我们 建议鉴定和过表达大环内酯类的正调节剂 生产在第二阶段，我们建议阻断竞争性代谢途径 和使用靶向插入突变的负调节子。最终我们 将创建一系列提高产量的产品， 或将它们联合收割机合并成一个 用于高水平大环内酯生产的FermaLogic菌株。

The macrolides are microbial natural products with many uses in clinical and veterinary medicine. Erythromycin is the best studied example of a macrolide antibiotic; rapamycin and FK506 are promising new immunosuppressant macrolides. The price and availability of macrolides depend on their production efficiency, and therefore, on the genetics of the producing strain. Recently, university studies have shown that increasing copy-number of regulatory antibiotic genes dramatically increases the level of production of model antibiotic compounds. FermaLogic scientists are familiar with the tools required to perform analogous experiments in macrolide-producing organisms. In phase one, we propose to identify and overexpress positive regulators of macrolide production. In phase two, we propose to block competing metabolic pathways and negative regulators using targeted insertion mutations. Ultimately, we will create a collection of yield-improvement products and license them separately to client organizations or combine them into a single FermaLogic strain for high-level macrolide production.