title: Overexpression of aveBIV leading to the improvement of 4'-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707.
abstract: The 4'-epidaunorubicin is the semisynthesis precursor of epirubicin which is a clinically useful antitumor drug thought to have slightly less cardiotoxicity than doxorubin. The 4'-epidaunorubicin was formed by overexpression of heterologous Streptomyces avermitilis aveBIV in Streptomyces coeruleorubidus SIPI-A0707 dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of daunorubicin. But there was a low-yield production of 4'-epidaunorubicin. In our study, product yields were enhanced considerably by increasing aveBIV gene copy number or changing means of aveBIV integration. The 4'-epidaunorubicin titer was improved by around threefold in the recombinant strain DYG1006 with the aveBIV increased threefold copy numbers. The transcript levels of aveBIV gene meet the expectation of fermentation levels of 4'-epidaunorubicin. The method described here provides the means to produce 4'-epidaunorubicin efficiently on an industrial scale.
authors.affiliation: State Key Lab of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Shanghai, 200040, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shao
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: Jing
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Chen
authors.forename: Shi-Dong
authors.initials: SD
authors.lastname: Kan
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Ji-An
authors.initials: JA
authors.lastname: Li
authors.forename: Dai-Jie
authors.initials: DJ
authors.lastname: Chen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C046084:3'-epidaunorubicin; D003630:Daunorubicin