Improvement of secondary metabolite production in Streptomyces by manipulating pathway regulation |
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Authors: | Yihua Chen Michael J Smanski Ben Shen |
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Institution: | (1) Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705-2222, USA;(2) Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI 53705-2222, USA;(3) Division of Pharmaceutical Sciences, University of Wisconsin National Cooperative Drug Discovery Group, and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave, Madison, WI 53705-2222, USA; |
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Abstract: | 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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