Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
Appl Microbiol Biotechnol. 2010 Mar;86(1):19-25. doi: 10.1007/s00253-009-2428-3. Epub 2010 Jan 21.
Titer improvement is a constant requirement in the fermentation industry. The traditional method of "random mutation and screening" has been very effective despite the considerable amount of time and resources it demands. Rational metabolic engineering, with the use of recombinant DNA technology, provides a novel, alternative strategy for titer improvement that complements the empirical method used in industry. Manipulation of the specific regulatory systems that govern secondary metabolite production is an important aspect of metabolic engineering that can efficiently improve fermentation titers. In this review, we use examples from Streptomyces secondary metabolism, the most prolific source of clinically used drugs, to demonstrate the power and utility of exploiting natural regulatory networks, in particular pathway-specific regulators, for titer improvement. Efforts to improve the titers of fredericamycin, C-1027, platensimycin, and platencin in our lab are highlighted.
效价提高是发酵工业的一项持续需求。尽管“随机突变和筛选”的传统方法需要大量的时间和资源，但它已经非常有效。理性的代谢工程，利用重组 DNA 技术，为效价提高提供了一种新颖的替代策略，补充了工业中使用的经验方法。对控制次生代谢产物生产的特定调节系统的操纵是代谢工程的一个重要方面，它可以有效地提高发酵效价。在这篇综述中，我们使用来自链霉菌次生代谢的例子，这是临床使用药物的最丰富来源，来说明利用天然调节网络，特别是途径特异性调节剂，来提高效价的威力和实用性。我们实验室在提高弗雷德里克霉素、C-1027、platensimycin 和 platencin 的效价方面所做的努力被强调了。
