NDLI: Proteomic approach to enhance doxorubicin production in panK-integrated Streptomyces peucetius ATCC 27952

Content Provider	Springer Nature Link
Author	Song, Eunjung Malla, Sailesh Yang, Yung Hun Lee, Kwangwon Kim, Eun Jung Lee, Hei Chan Sohng, Jae Kyung Oh, Min Kyu Kim, Byung Gee
Copyright Year	2011
Abstract	Biosynthesis of polyketide compounds depends upon the starter and extender units of coenzyme A derivatives of carboxylic acids present in the host organism. To increase the coenzyme A (CoA) pool, pantothenate kinase (panK) gene from Escherichia coli was integrated into S. peucetius ATCC 27952 (panK-integrated strain, BG200), which resulted in increase in aglycone polyketide ε-rhodomycinone (RHO), but decrease in the desired product, i.e., doxorubicin (DXR). To reduce RHO accumulation by synthesizing daunorubicin (DNR) from RHO more efficiently, glycosyltransferase (dnrQS) was overexpressed (pIBR25::dnrQS in panK-integrated strain, BG201). However, DnrQS overexpression still resulted in less production of DXR compared with the parental strain. To understand the results in detail by investigating the proteome changes in the panK-integrated strain, two-dimensional (2D) gel electrophoresis was performed. Among the several proteins that are up- or downregulated in BG200, efflux protein DrrA was our main target of interest, because it is directly related to DXR/DNR production in S. peucetius. DXR transporter DrrAB was additionally introduced in BG200 to enhance secretion of toxic DXR. Compared with S. peucetius ATCC 27952, BG204 (pIBR25::drrAB in panK-integrated strain), produced two times higher amount of DXR, which is 9.4-fold higher than that of panK-integrated strain BG200. The results show that the proteomic approach is quite useful in host development of Streptomyces and understanding cell physiology for antibiotic production.
Starting Page	1245
Ending Page	1253
Page Count	9
File Format	PDF
ISSN	13675435
Journal	Journal of Industrial Microbiology and Biotechnology
Volume Number	38
Issue Number	9
e-ISSN	14765535
Language	English
Publisher	Springer-Verlag
Publisher Date	2011-02-10
Publisher Place	Berlin, Heidelberg
Access Restriction	Subscribed
Subject Keyword	Streptomyces peucetius 2-DE nLC-MS/MS Pantothenate kinase Genetic Engineering Microbiology Biotechnology Inorganic Chemistry Biochemistry Bioinformatics
Content Type	Text
Resource Type	Article
Subject	Medicine Bioengineering Applied Microbiology and Biotechnology Biotechnology

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