METABOLIC ENGINEERING OF ANTIBIOTIC BIOSYNTHESIS

描述：抗生素生产的代谢工程 放线菌是在制药工业中常规进行的， 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 已经使用基本上相同的方法进行了重要的程序 在过去的50年里，经验主义的突变和筛选过程。 最近 这些分子遗传操作的技术进展 具有重要商业价值的微生物， 代谢工程的过程从一个合理的设计 perspective.红霉素生产菌，多孢菌属 Erythria是开发这项技术的理想系统， 红霉素是一种经过充分研究的分子， 重组操作，并且需要改进重组操作。 这种化合物的生产，由于越来越多的半， 目前进入市场的红霉素的合成衍生物。 在初步工作中，FermaLogic的科学家们发现了强大的 一个积极的调控基因影响生产水平的证据 红霉素的五倍，并已绘制出其在 265 kb的基因组区域。 该提案描述了一项战略， 寻找可能的调控基因， 这些操作将导致最终设计红霉素， 超级高产菌株 拟议商业应用：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