文摘
A gene designated jadI from the jadomycin B producer Streptomyces venezuelae has homology tothe tetracenomycin pathway tcmI gene and encodes a putative cyclase for angucyclinone biosynthesis. Expressionin Streptomyces lividans of a jadomycin (jad) gene cassette composed of the minimal polyketide synthase(PKS, jadABC), a cyclase (jadD), a ketoreductase (jadE), and jadI leads to production of several yellowcompounds in liquid culture. Rabelomycin (1), a known angucyclinone, results from dehydration and oxidationof a new product, UWM6, isolated from the culture extracts. Characterization of UWM6 by UV, MS, andNMR analyses revealed a new angucyclinone structure, 4-hydroxy-12bH-12-deoxyrabelomycin. Productionof these angucyclinones occurs only when jadI is present in the cassette, suggesting an essential cyclasephenotype for this gene. Engineered replacement of jadI in the jad cassette with the tcmI cyclase gene, andsimilar replacement of tcmI in a functional tcm PKS cassette with jadI, leads to the same set of aromaticdecapolyketides produced by either cassette in the absence of jadI. From these results we conclude that bothcyclases are nonfunctional out of their normal context.
