Dissecting and exploiting intermodular communication in polyketide synthases
Dissecting and exploiting intermodular communication in polyketide synthases
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DOI：
10.1126/science.284.5413.482
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发表时间：
1999-04-16
期刊：
影响因子：
56.9
通讯作者：
Khosla, C
中科院分区：
文献类型：
--
作者：
Gokhale, RS;Tsuji, SY;Khosla, C
模块化聚酮酶通过装配线机制催化重要的药用天然产物的生物合成。虽然这些megasynthases显示非常精确的整体选择性，我们表明，它们的组成模块是非常宽容的对不同的传入酰基链。通过对多肽内部和之间存在的接头进行适当的工程改造，可以利用这种耐受性来促进生物合成中间体在非天然连接的模块之间的转移。这种蛋白质工程策略也提供了深入了解模块化聚酮酶的进化。
Modular polyketide synthases catalyze the biosynthesis of medicinally important natural products through an assembly-line mechanism. Although these megasynthases display very precise overall selectivity, we show that their constituent modules are remarkably tolerant toward diverse incoming acyl chains. By appropriate engineering of linkers, which exist within and between polypeptides, it is possible to exploit this tolerance to facilitate the transfer of biosynthetic intermediates between unnaturally linked modules. This protein engineering strategy also provides insights into the evolution of modular polyketide synthases.