Type I modular polyketide synthases are homodimeric multidomain assembly line enzymes that synthesize a variety of polyketide natural products by performing polyketide chain extension and β-keto group modification reactions. We determined the 2.4-angstrom-resolution x-ray crystal structure and the 3.1-angstrom-resolution cryo–electron microscopy structure of the Lsd14 polyketide synthase, stalled at the transacylation and condensation steps, respectively. These structures revealed how the constituent domains are positioned relative to each other, how they rearrange depending on the step in the reaction cycle, and the specific interactions formed between the domains. Like the evolutionarily related mammalian fatty acid synthase, Lsd14 contains two reaction chambers, but only one chamber in Lsd14 has the full complement of catalytic domains, indicating that only one chamber produces the polyketide product at any given time.

中文翻译：

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模块化聚酮合酶包含两个异步操作的反应室

I 型模块化聚酮化合物合酶是同二聚体多结构域装配线酶，通过进行聚酮化合物链延伸和 β-酮基修饰反应合成多种聚酮化合物天然产物。我们确定了 Lsd14 聚酮合酶的 2.4 埃分辨率的 X 射线晶体结构和 3.1 埃分辨率的低温电子显微镜结构，分别在转酰基化和缩合步骤中停止。这些结构揭示了组成域如何相对于彼此定位，它们如何根据反应循环中的步骤重新排列，以及域之间形成的特定相互作用。与进化相关的哺乳动物脂肪酸合酶一样，Lsd14 包含两个反应室，但 Lsd14 中只有一个反应室具有完整的催化结构域，