Orthogonal protein interactions in spore pigment producing and antibiotic producing polyketide synthases

Orthogonal protein interactions in spore pigment producing and antibiotic producing polyketide synthases
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DOI:
10.1038/ja.2005.91
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发表时间:
2005-10-01
影响因子:
3.3
通讯作者:
Tang, Y
Tang, Y
中科院分区:
医学4区
文献类型:
--
作者:
Lee, TS;Khosla, C;Tang, Y

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放线菌在其生命周期中通过使用 II 型聚酮合酶 (PKS) 产生抗生素和孢子色素。每个 PKS 至少由酮合酶异二聚体和酰基载体蛋白组成。酰基载体蛋白已被证明可以在产生不同抗生素的 II 型 PKS 之间互换。令人惊讶的是,我们发现来自抗生素生产途径的酮合成酶和酰基载体蛋白与来自孢子色素途径的酮合成酶和酰基载体蛋白之间存在根本的不相容性。尽管抗生素 PKS 可以与来自孢子色素途径的酰基载体蛋白相互作用,但孢子色素 PKS 无法识别来自聚酮化合物抗生素途径的酰基载体蛋白。这一观察结果提供了对该细菌家族成员发挥天然产物生物合成特异性的关键机制的见解。
The actinomycetes produce antibiotics as well as spore pigments during their life cycle by using Type II polyketide synthases (PKSs). Each PKS minimally consists of a ketosynthase heterodimer and an acyl carrier protein. The acyl carrier protein has been shown to be interchangeable among different antibiotic producing Type II PKSs. Surprisingly, we have discovered a fundamental incompatibility between the ketosynthases and acyl carrier proteins from antibiotic producing pathways and those from spore pigment pathways. Although antibiotic PKSs can interact with acyl carrier proteins from spore pigment pathways, spore pigment PKSs are unable to recognize acyl carrier proteins from polyketide antibiotic pathways. This observation provides an insight into a critical mechanism by which natural product biosynthetic specificity is exercised by members of this bacterial family.