Overexpression of aveBIV leading to the improvement of 4′-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707

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 coeruleorub...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2010-07, Vol.87 (3), p.1057-1064
Main Authors: Shao, Lei, Huang, Jia, Jing, Lan, Chen, Ji-Ye, Kan, Shi-Dong, Wang, Min, Li, Ji-An, Chen, Dai-Jie
Format: Article
Language:English
Subjects:
Antibiotics
Applied Genetics and Molecular Biotechnology
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological and medical sciences
Biomedical and Life Sciences
Biosynthesis
Biotechnology
Cancer
Cloning
Daunorubicin
Daunorubicin - metabolism
E coli
Epidaunorubicin
Fermentation
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation, Bacterial
Gene replacement
Genetic engineering
Life Sciences
Medical research
Microbial Genetics and Genomics
Microbiology
Overexpression
Pharmaceutical industry
Pharmacology
Plasmids
Streptomyces
Streptomyces - genetics
Streptomyces - metabolism
Studies
Toxicity
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Summary: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.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-010-2541-3