Kuhstoss S, Huber M, Turner J R, Paschal J W, Rao R N
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Gene. 1996 Dec 12;183(1-2):231-6. doi: 10.1016/s0378-1119(96)00565-3.
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.
聚酮化合物普拉特内酯和泰乐内酯的内酯环是由乙酸盐、丙酸盐和丁酸盐衍生的前体缩合而成。构建了一种杂合的泰乐内酯/普拉特内酯合酶，以确定底物的选择是否由聚酮合酶编程，并确定在普拉特内酯合成第一步中使用的正常底物以外的底物是否可以掺入最终的聚酮化合物中。在这项工作中，我们报告成功地用丙酸盐取代了普拉特内酯合成第一步中正常使用的乙酸盐。这一结果表明，聚酮合酶在特定步骤选择特定底物，并提供了有力证据，证明底物选择是由大型多功能聚酮合酶的酰基转移酶结构域编程的。
