Iso-migrastatin titer improvement in the engineered <Emphasis Type="Italic">Streptomyces lividans</Emphasis> SB11002 strain by optimization of fermentation conditions |
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Authors: | Xueyun Wu Dong Yang Xiangcheng Zhu Zhiyang Feng Zhengbin Lv Yaozhou Zhang Ben Shen Zhinan Xu |
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Institution: | (1) Department of Chemical and Biological Engineering, Institute of Bioengineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China;(2) Division of Pharmaceutical Science, School of Pharmacy, University of Wisconsin–Madison, 777 Highland Avenue, Madison, WI 53705, USA; |
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Abstract: | The heterologous production of iso-migrastatin (iso-MGS) was successfully demonstrated in an engineered S. lividans SB11002 strain, which was derived from S. lividans K4-114, following introduction of pBS11001, which harbored the entire mgs biosynthetic gene cluster. However, under similar fermentation conditions, the iso-MGS titer in the engineered strain was
significantly lower than that in the native producer — Streptomyces platensis NRRL 18993. To circumvent the problem of low iso-MGS titers and to expand the utility of this heterologous system for iso-MGS
biosynthesis and engineering, systematic optimization of the fermentation medium was carried out. The effects of major components
in the cultivation medium, including carbon, organic and inorganic nitrogen sources, were investigated using a single factor
optimization method. As a result, sucrose and yeast extract were determined to be the best carbon and organic nitrogen sources,
resulting in optimized iso-MGS production. Conversely, all other inorganic nitrogen sources evaluated produced various levels
of inhibition of iso-MGS production. The final optimized R2YE production medium produced iso-MGS with a titer of 86.5 mg/L,
about 3.6-fold higher than that in the original R2YE medium, and 1.5 fold higher than that found within the native S. platensis NRRL 18993 producer. |
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