title: New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae.
abstract: A mutant strain of Streptomyces venezuelae was engineered by deletion of the entire gene cluster related to biosynthesis of the endogenous deoxysugar (TDP-D-desosamine) and replacement with genes required for biosynthesis of an intermediate sugar (TDP-4-keto-6-deoxy-D-glucose) or an exogenous sugar (TDP-D-olivose), from the oleandomycin and urdamycin deoxysugar pathways. The 'sugar-flexible' glycosyltransferase (DesVII) was able to attach the intermediate sugar and the new sugar to both 12- and 14-membered macrolactones thus producing quinovose or olivose glycosylated 10-deoxymethynolide and narbonolide, respectively. In addition, hydroxylated analogs of the new metabolites were detected. These results demonstrate a successful attempt of engineering the deoxysugar pathway for generation of novel hybrid macrolide antibiotics.
authors.affiliation: Interdisciplinary Program of Biochemical Engineering and Biotechnology, Seoul National University, San 56-1, Shilim-dong, Gwanak-gu, Seoul 151-742, South Korea.
authors.forename: Jay Sung Joong
authors.initials: JS
authors.lastname: Hong
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Cha Yong
authors.initials: CY
authors.lastname: Choi
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.forename: Yeo Joon
authors.initials: YJ
authors.lastname: Yoon
mesh_terms: D017353:Gene Deletion; D005818:Genetic Engineering; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification*; D010957:Plasmids / Q000235:genetics; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D018942:Macrolides; C008517:methymycin; C003145:picromycin