Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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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)
  • Published : 2008.01.31
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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

References

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