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Genetically Engineered Biosynthesis of Macrolide Derivatives Including 4-Amino-4,6-Dideoxy-L-Glucose from Streptomyces venezuelae YJ003-OTBP3  

Pageni, Binod Babu (Institute of Biomolecule Reconstruction(IBR), Department of Pharmaceutical Engineering, SunMoon University)
Oh, Tae-Jin (Institute of Biomolecule Reconstruction(IBR), Department of Pharmaceutical Engineering, SunMoon University)
Liou, Kwang-Kyoung (Institute of Biomolecule Reconstruction(IBR), Department of Pharmaceutical Engineering, SunMoon University)
Yoon, Yeo-Joon (Divison of Nano Sciences and Department of Chemistry, Ewha Womans University)
Sohng, Jae-Kyung (Institute of Biomolecule Reconstruction(IBR), Department of Pharmaceutical Engineering, SunMoon University)
Publication Information
Journal of Microbiology and Biotechnology / v.18, no.1, 2008 , pp. 88-94 More about this Journal
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+ $Na^+$] 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 a 14-membered ring aglycon (narbonolide, 2). These results suggest a successful engineering of a deoxysugar pathway to generate novel hybrid macrolide derivatives, including deoxyaminosugar.
Keywords
4-Amino-4,6-dideoxy-L-glucose; glycosyitransferase; heterologous expression; hybrid antibiotics; Streptomyces venezuelae YJ003;
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