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Doxorubicin Productivity Improvement by the Recombinant Streptomyces peucetius with High-Copy Regulatory Genes Cultured in the Optimized Media Composition


Doxorubicin is a clinically important anticancer polyketide compound that is typically produced by Streptomyces peucetius var. caesius. To improve doxorubicin productivity by S. peucetius, a doxorubicin pathway-specific regulatory gene, dnrI, was cloned into a high-copy-number plasmid containing a catechol promoter system. The S. peucetius containing the recombinant plasmid exhibited approximately 9.5-fold higher doxorubicin productivity compared with the wild-type S. peucetius. The doxorubicin productivity by this recombinant S. peucetius strain was further improved through the optimization of culture media composition. Based on the Fractional Factorial Design (FFD), cornstarch, $K_2HPO_4$, and $MgSO_4$ were identified to be the key factors influencing doxorubicin productivity. The Response Surface Method (RSM) results based on 20 independent culture conditions with varying amounts of key factors predicted the highest theoretical doxorubicin productivity of 11.1 mg/l with corn starch of 46.33 g/l, $K_2HPO_4$ of 4.63 g/l, and $MgSO_4$ of 9.26 g/l. The doxorubicin productivity of the recombinant S. peucetius strain with the RSM-based optimized culture condition was experimentally verified to be 11.46 mg/l, which was approximately 30.8-fold higher productivity compared with the wild-type S. peucetius without culture media optimization.

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이 논문을 인용한 문헌 (10)

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  9. 2009. "" Journal of microbiology and biotechnology, 19(2): 136~139 
  10. Kim, Chang-Young ; Noh, Jun-Hee ; Lee, Han-Na ; Kim, Eung-Soo 2009. "Functional Analysis of an Antibiotic Regulatory Gene, afsR2 in S. lividans through DNA microarray System" KSBB Journal, 24(3): 259~266 


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