期刊
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
卷 86, 期 1, 页码 19-25出版社
SPRINGER
DOI: 10.1007/s00253-009-2428-3
关键词
Titer improvement; Streptomyces; Secondary metabolite; Regulator; Biosynthesis
资金
- National Institutes of Health (NIH) [CA78747, CA106150, CA113297, T32 GM008347]
- NATIONAL CANCER INSTITUTE [R01CA106150, U19CA113297, R01CA078747] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008347] Funding Source: NIH RePORTER
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.
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