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Doxorubicin is a clinically important anticancerpolyketide compound that is typically produced by Streptomycespeucetius var. caesius. To improve doxorubicin productivityby S. peucetius, a doxorubicin pathway-specific regulatory gene,dnrI, was cloned into a high-copy-number plasmid containinga catechol promoter system. The S. peucetius containing therecombinant plasmid exhibited approximately 9.5-fold higherdoxorubicin productivity compared with the wild-type S.peucetius. The doxorubicin productivity by this recombinantS. peucetius strain was further improved through the optimizationof culture media composition. Based on the Fractional FactorialDesign (FFD), cornstarch, K2HPO4, and MgSO4 were identifiedto be the key factors influencing doxorubicin productivity.The Response Surface Method (RSM) results based on 20independent culture conditions with varying amounts of keyfactors predicted the highest theoretical doxorubicin productivityof 11.1 mg/l with corn starch of 46.33 g/l, K2HPO4 of 4.63 g/l,and MgSO4 of 9.26 g/l. The doxorubicin productivity ofthe recombinant S. peucetius strain with the RSM-basedoptimized culture condition was experimentally verified tobe 11.46 mg/l, which was approximately 30.8-fold higherproductivity compared with the wild-type S. peucetius withoutculture media optimization.

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