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KMID : 0545120080180010088
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Journal of Microbiology and Biotechnology
2008 Volume.18 No. 1 p.88 ~ p.94
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Genetically Engineered Biosynthesis of Macrolide Derivatives Including 4- Amino-4,6-Dideoxy-L-Glucose from Streptomyces venezuelae YJ003-OTBP3
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Pageni Binod Babu
Oh Tae-Jin
Liou Kwangkyoung
Yoon Yeo-Joon
Sohng Jae-Kyung
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Abstract
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Two sugar biosynthetic cassette plasmids were used to direct the biosynthesis of a deoxyaminosugar. The pOTBP1 plasmid containing TDP-glucose synthase (desIII), TDP-glucose-4,6-dehydratase (desIV), and glycosyltransferase (desVII/desVIII) was constructed and transformed into S. venezuelae YJ003, a strain in which the entire gene cluster of desosamine biosynthesis is deleted. The expression plasmid pOTBP3 containing 4-aminotransferase (gerB) and 3,5-epimerase (orf9) was transformed again into S. venezuelae YJ003- OTBP1 to obtain S. venezuelae YJ003-OTBP3 for the production of 4-amino-4,6-dideoxy-L-glucose derivatives. The crude extracts obtained from S. venezuelae ATCC 15439, S. venezuelae YJ003, and S. venezuelae YJ003-OTBP3 were further analyzed by TLC, bioassay, HPLC, ESI/MS, LC/MS, and MS/MS. The results of our study clearly shows that S. venezuelae YJ003-OTBP3 constructs other new hybrid macrolide derivatives including 4-amino-4,6-dideoxy-L-glycosylated YC-17 (3, [M+ Na+] m/z=464.5), methymycin (4, m/z=480.5), novamethymycin (6, m/z=496.5), and pikromycin (5, m/z=536.5) from a 12- membered ring aglycon (10-deoxymethynolide, 1) and 14-membered ring aglycon (narbonolide, 2). These results suggest a successful engineering of a deoxysugar pathway to generate novel hybrid macrolide derivatives, including deoxyaminosugar.
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KEYWORD
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4-Amino-4, 6-dideoxy-L-glucose, glycosyltransferase, heterologous expression, hybrid antibiotics, Streptomyces venezuelae YJ003
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