New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae.
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.
Hong
Jay Sung Joong
JS
Interdisciplinary Program of Biochemical Engineering and Biotechnology, Seoul National University, San 56-1, Shilim-dong, Gwanak-gu, Seoul 151-742, South Korea.
Park
Sung Hee
SH
Choi
Cha Yong
CY
Sohng
Jae Kyung
JK
Yoon
Yeo Joon
YJ
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
D018942:Macrolides; C008517:methymycin; C003145:picromycin