Open AccessNew olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae
Author(s) -
Hong Jay Sung Joong,
Park Sung Hee,
Choi Cha Yong,
Sohng Jae Kyung,
Yoon Yeo Joon
Publication year - 2004
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2004.tb09781.x
Subject(s) - oleandomycin , glycosyltransferase , biosynthesis , streptomyces , biochemistry , sugar , gene cluster , mutant , strain (injury) , polyketide synthase , streptomycetaceae , chemistry , polyketide , biology , gene , actinomycetales , antibiotics , bacteria , genetics , anatomy , erythromycin
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.