Production of a novel polyketide through the construction of a hybrid polyketide synthase

被引:99
作者
Kuhstoss, S
Huber, M
Turner, JR
Paschal, JW
Rao, RN
机构
[1] Lilly Research Laboratories, Lilly Corporate Center, Indianapolis
关键词
macrolide; platenolide; spiramycin; tylactone; tylosin; Streptomyces; gene fusion;
D O I
10.1016/S0378-1119(96)00565-3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The lactone rings of the polyketides platenolide and tylactone are synthesized by condensation of acetate-, proprionate-, and butyrate-derived precursors. A hybrid tylactone/platenolide synthase was constructed to determine if the choice of substrate is programmed by the polyketide synthase and to ascertain if a substrate different than that normally used in the first step of platenolide synthesis could be incorporated into the final polyketide. In this work, we report the successful incorporation of a propionate in place of the acetate normally used in the first step of platenolide synthesis. This result demonstrates that polyketide synthases choose a particular substrate at defined steps and provides strong evidence that substrate choice is programmed by the acyl transferase domain of a large, multifunctional polyketide synthase.
引用
收藏
页码:231 / 236
页数:6
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