碳源调控珍贵束丝放线菌中抗癌药安丝菌素生物合成的研究

Ansamitocins are an important class of anticancer antibiotics. In Actinosynnema pretiosum, different carbon sources (glucose, fructose, galactose, xylose and sucrose) were found to have large effects on the production of ansamitocin. Glucose was the best carbon source for the growth of A. pretiosum, and fructose was favorable for ansamitocin production. This project is based on the precious work, and combine with signaling molecule-cAMP, enzymology, gene overexpression, gene knockout, gene transcription, to clarify the effects of important nutritional factor- carbon source on ansamitocin biosynthesis , and to explain a broad spectrum of carbon-glucose to inhibit mechanisms of ansamitocin biosynthesis. The inner mechanism was further investigated for A. pretiosum cells grown on either glucose or fructose to explore the relationship between the different carbon sources metabolism and ansamitocin biosynthesis. The completion of this research will help to construct recombinant strains to a produce highly efficient ansamitocin in glucose medium. It will be perspective to promote ansamitocin application as a new anticancer antibiotic in the medical field, and also for related species to provide reference in metabolism engineering.

安丝菌素(ansamitocins)是一类重要的抗癌抗生素，在珍贵束丝放线菌橙色变种(Actinosynnema pretiosum)中，发现不同碳源(葡萄糖，果糖，半乳糖，木糖和蔗糖)对生产安丝菌素产生很大的差异，结果表明葡萄糖最利于菌体生长，果糖最利于菌体合成安丝菌素。本研究拟通过对珍贵橙色束丝放线菌结合信号分子cAMP、酶学、基因的敲除、基因过表达、基因转录的考察，阐明在发酵培养过程中重要营养因子碳源对安丝菌素生物合成的差异的影响机制，解析广谱碳源葡萄糖抑制安丝菌素合成的内在机理。本研究的完成，有助于构建一个以葡萄糖为碳源高效生产安丝菌素的重组菌株，促进安丝菌素作为一个新的抗癌抗生素在医药领域的应用，也为相关菌属的代谢工程改造提供借鉴。