Stimulation of polyketide metabolism in Streptomyces fradiae by tylosin and its glycosylated precursors

泰乐菌素 弗氏链霉菌 聚酮 生物化学 还原酶 生物合成 苷元 链霉菌 生物 化学 放线菌 立体化学 抗生素 细菌 遗传学 糖苷
作者
S. Fish,Eric Cundliffe
出处
期刊:Microbiology [Microbiology Society]
卷期号:143 (12): 3871-3876 被引量:42
标识
DOI:10.1099/00221287-143-12-3871
摘要

Three glycosyltransferases are involved in tylosin biosynthesis in Streptomyces fradiae. The first sugar to be added to the polyketide aglycone (tylactone) is mycaminose and the gene encoding mycaminosyltransferase is orf2 * ( tylM2 ). However, targeted disruption of orf2 * did not lead to the accumulation of tylactone under conditions that normally favour tylosin production; instead, the synthesis of tylactone was virtually abolished. This may, in part, have resulted from a polar effect on the expression of genes downstream of orf2 * . particularly orf4 * ( ccr ) which encodes crotonyl-CoA reductase, an enzyme that supplies 4-carbon extender units for polyketide metabolism. However, that cannot be the entire explanation, since tylosin production was restored at about 10% of the wild-type level when orf2 * was re-introduced into the disrupted strain. When glycosylated precursors of tylosin were fed to the disrupted strain, they were converted to tylosin, confirming that two of the three glycosyltransferase activities associated with tylosin biosynthesis were still intact. Interestingly, however, tylactone also accumulated under such conditions and, to a much lesser extent, when tylosin was added to similar fermentations. It is concluded that glycosylated macrolides exert a pronounced positive effect on polyketide metabolism in S. fradiae.
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