원문정보
초록
영어
To develop a system for combinatorial biosynthesis of glycosylated macrolides, Streptomyces venezuelae was genetically manipulated to be deficient in production of its macrolide antibiotics by deletion of the entire pikromycin biosynthetic gene cluster. The resulting strain was designated YJ028. In order to endow the structural diversity to tylosin analogs by modification of C-23 postion of 5-O-mycaminosyl tylonolide (OMT), and identify the biosynthetic pathway of 6-deoxyallose as a part of tylosin formation in S. fradiae, TDP-D-quinovose or proposed TDP-D-6-deoxyallose biosynthetic pathway was expressed. The expression of TDP-D-quinovose pathway in conjunction with TylN in YJ028 supplemented with OMT resulted in the failure to generate quinovosyl OMT. On the other hand, 6-deoxyallosyl OMT was successfully biosynthesized in YJ028 expressing tylD, tylJ, desIII, and desVI fed with OMT. These results showed that the stringent substrate specificity of TylN glycosyltransferase toward non-native deoxysugar, especially TDP-Dquinovose as well as introduction of tylJ and tylD together with desIII/desVI was sufficient for the biosynthesis of 6-deoxyallose.