ERYTHROMYCIN ANALOGS BY METABOLIC ENGINEERING

描述（改编自申请）：新型分子遗传学 现在正在使用一些方法来产生抗生素结构， 不能通过化学合成成本有效地生产。 新 “组合生物合成”和分子生物学方法 “代谢工程”利用放线菌分子的特殊工具 遗传学和不断增长的克隆和测序抗生素 生物合成途径基因 已经建立了许多结构， 和至少一种定制结构的6-脱氧红霉素， 生产出的化合物性能优于母体化合物。 的 申请人建议扩大新结构的潜在数量， 可以通过开发新的基因转移系统来创造， 使其他14元环大环内酯类抗生素类似的微生物 红霉素。 他们建议克隆现有的新的同源物， “剪裁”酶，并将它们重新组合以产生新的结构， 提高化学或生物活性， 开发新的化学中间体和可能的新抗生素。 拟定商业应用： 我们建议创造新的类似物的14元大环内酯 具有潜在治疗价值的抗生素， 化学中间体或新的人类或兽医治疗剂。的 大环内酯类抗生素的市场是在数亿美元， 年收入，而且还在增长。我们的商业潜力 新结构意义重大。

DESCRIPTION (Adapted from the application): Novel molecular genetic methods are now being used to generate antibiotic structures that could not be cost-effectively produced through chemical synthesis. The new methods of "combinatorial biosynthesis" and molecular biological "metabolic engineering" use the special tools of Actinomycete molecular genetics and the growing collection of cloned and sequenced antibiotic biosynthetic pathway genes. Already, many structures have been created and at least one tailored structure 6-deoxyerythromycin, has been produced with improved properties over the parent compound. The applicant proposes to expand the potential number of new structures that can be created through the development of new gene transfer systems in organisms that make other 14-member ring macrolide antibiotics similar to erythromycin. They propose to clone new homologs of existing "tailoring" enzymes and inactivate them to generate new structures with improved chemical or biological activity that could lead to the development of new chemical intermediates and possibly new antibiotics. PROPOSED COMMERCIAL APPLICATION: We are proposing to create novel analogs of 14-membered macrolide antibiotics with potential therapeutic value that will be useful as new chemical intermediates or new human or veterinary therapeutics. The market for macrolide antibiotics is in the hundreds of millions of dollars per year and is still growing. The commercial potential for our new structures is significant.