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Genetically Engineered Biosynthesis of Macrolide Derivatives Including 4- Amino-4,6-Dideoxy-L-Glucose from Streptomyces venezuelae YJ003-OTBP3
1Institute of Biomolecule Reconstruction (IBR), Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Korea, 2Division of Nano Sciences and Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
J. Microbiol. Biotechnol. 2008; 18(1): 88-94
Published January 28, 2008
Copyright © The Korean Society for Microbiology and Biotechnology.
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J. Microbiol. Biotechnol. 2008; 18(1): 88-94
Published online January 28, 2008
Copyright © The Korean Society for Microbiology and Biotechnology.
Genetically Engineered Biosynthesis of Macrolide Derivatives Including 4- Amino-4,6-Dideoxy-L-Glucose from Streptomyces venezuelae YJ003-OTBP3
Pageni, Binod Babu 1, Tae-Jin Oh 1, Kwangkyoung Liou 1, Yeo Joon Yoon 2 and Jae Kyung Sohng 1*
1Institute of Biomolecule Reconstruction (IBR), Department of Pharmaceutical Engineering, SunMoon University, Asan 336-708, Korea, 2Division of Nano Sciences and Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
Abstract
Two sugar biosynthetic cassette plasm ids 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+
Keywords: 4-Amino-4,6-dideoxy-L-glucose, glycosyltransferase, heterologous expression, hybrid antibiotics, Streptomyces venezuelae YJ003