METABOLIC ENGINEERING OF ANTIBIOTIC BIOSYNTHESIS

描述：抗生素生产的代谢工程 放线菌在制药行业中是常规操作，以 提高产量，从而降低生产成本 重要的药物化合物，包括抗生素。这 重要的程序已经使用基本上相同的 过去50年的经验变异和筛选过程。近期 这些基因的分子遗传操作技术进展 具有重要商业意义的微生物现在使人们有可能接近 代谢工程从基本原理设计的过程 透视。红霉素产生菌--糖多孢菌 是开发这项技术的理想系统，因为 红霉素是一种研究得很好的分子，生物体适合 重组操作，并且需要改进 这种化合物的生产是由于半成品的数量不断增加 红霉素的合成衍生物目前正在进入市场。 在初步工作中，费马逻辑的科学家们已经发现了强大的 影响产量水平的积极调控基因的证据 红霉素是红霉素的五倍，并绘制了它在 基因组全长265kb。这份提案描述了一项战略， 找到推测的调控基因，并利用它进行进一步的理性分析 将导致红霉素最终设计的操作 超高产菌株。 建议的商业应用：不可用

DESCRIPTION: Metabolic engineering of antibiotic producing actinomycetes is performed routinely in the pharmaceutical industry to increase the yield and thereby reduce the cost of production of important pharmaceutical compounds, including antibiotics. This important procedure has been performed using essentially the same empirical mutate-and-screen process for the past 50 years. Recent technical advances in the molecular genetic manipulation of these commercially important microorganisms now make it possible to approach the process of metabolic engineering from a rationale design perspective. The erythromycin producing organisms, Saccharopolyspora erythrea, is an ideal system for developing this technology because erythromycin is a well-studied molecule, the organism lends itself to recombinant manipulations, and there is a need for improving the production of this compound due to the increasing number of semi- synthetic derivatives of erythromycin currently entering the market. In preliminary work, FermaLogic scientists have uncovered strong evidence for a positive regulatory gene that affects production levels of erythromycin by a factor of five and have mapped its location within a genomic region of 265 kb. This proposal describes a strategy for finding the presumed regulatory gene and using it for further rational manipulations that will lead to the eventual design of an erythromycin super-producing strain. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE