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영어

Tylosin is a 16-membered macrolide antibiotics produced by Streptomyces fradiae, composed of a branched lactone ring, tylactone and three deoxysugars, mycinose, mycaminose and mycarose. Of these different deoxysugars, mycinose is attached to C-23 position of tylactone. In
this study, the mycinose biosynthetic pathway was identified through the heterologous expression of several gene sets in an engineered strain of Streptomyces venezuelae. A plasmid harboring TDPdeoxyallose biosynthetic gene set (tylD-tylJ-tylN-desIII-desIV) was
constructed and introduced into the S. venezuelae YJ028 bearing a deletion of native pikromycin polyketide synthase and desosamine gene cluster. As a result, deoxyallosyl-OMT and deoxyallosyl-DMT were produced from 5-O-mycaminosyl tylonolide (OMT) and demycinosyl tylosin (DMT), respectively. In addition, expression of TDP-deoxyallose biosynthetic genes plus three different sets of methyltransferase genes tylE and tylF (tylE, tylF and tylE-tylF) in the
S. venezuelae YJ028 supplemented with OMT and DMT, led to the production of 2'''-or/and 3'''-methyldeoxylallosyl OMT and 2'''-or/and 3'''-methyldeoxylallosyl DMT, respectively. These results describe more precise mycinose biosynthetic pathway and biosynthetic routes
to tylosin of S. fradiae.