Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described “turnstile” mechanism for transient gating of active sites along the assembly line.

中文翻译：

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绘制装配线聚酮化合物合酶模块的催化构象

装配线聚酮化合物合酶，例如 6-脱氧赤藓糖醇 B 合酶 (DEBS)，是大型酶工厂，因其生产特定和复杂聚酮化合物产品的能力而备受推崇。通过在定义的线性序列中跨多个活性位点引导蛋白质连接的底物，这些酶促进了程序化的小分子合成，理论上可以利用这些合成来获得无数的聚酮化合物产物结构。使用低温电子显微镜研究 DEBS 模块 1，我们提出了一个描述这种底物通道现象的结构模型。我们完整模块的 3.2 到 4.3 埃分辨率结构揭示了关键的域-域接口并突出了意想不到的模块不对称性。