Staunton J
Department of Chemistry, University of Cambridge, UK.
Curr Opin Chem Biol. 1998 Jun;2(3):339-45. doi: 10.1016/s1367-5931(98)80007-0.
Modular polyketide synthases that produce many clinically important natural products such as erythromycins and lovastatins have been engineered in many ways to produce novel natural products. The structural variations have included alterations to the substituents on the macrolide ring, including the starter acid residue, using either semi-synthetic methodology or genetic engineering. It is now also possible to produce shorter polyketide chains that are released either as lactone rings (6-, 8-, 12- and 14-membered rings) or linear products. The strategies for engineering polyketide synthases to produce specific natural products are now well established. Several of the macrolides produced recently have been elaborated to produce novel antibiotics.
能够产生许多具有临床重要性的天然产物（如红霉素和洛伐他汀）的模块化聚酮合酶已通过多种方式进行改造，以生产新型天然产物。结构上的变化包括使用半合成方法或基因工程对大环内酯环上的取代基（包括起始酸残基）进行改变。现在也能够生产较短的聚酮链，这些聚酮链以内酯环（6元、8元、12元和14元环）或线性产物的形式释放。改造聚酮合酶以生产特定天然产物的策略现已成熟。最近生产的几种大环内酯已被进一步加工以生产新型抗生素。
