美国德克萨斯大学埃尔帕索分校Chu-Young Kim、美国康奈尔大学J. Christopher Fromme团队合作取得最新进展。他们表明模块化聚酮合酶包含两个异步操作的反应室。这一研究成果于2021年11月5日发表在国际顶尖学术期刊《科学》上。

他们确定了 Lsd14 聚酮化合物合酶的 2.4 埃分辨率 X 射线晶体结构和 3.1 埃分辨率冷冻电镜结构，分别在酰基转移和缩合步骤中停滞。这些结构揭示了组成结构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，以及结构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，表明在任何给定时间只有一个反应室产生聚酮化合物产物。

据悉，I 型模块化聚酮合酶是同型二聚体多结构域装配线酶，通过进行聚酮链延长和 β-酮基修饰反应合成多种聚酮天然产物。

附：英文原文

Title: Modular polyketide synthase contains two reaction chambers that operate asynchronously

Author: Saket R. Bagde, Irimpan I. Mathews, J. Christopher Fromme, Chu-Young Kim

Issue&Volume: 2021-11-05

Abstract: 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.

DOI: abi8532

Source: https://www.science.org/doi/10.1126/science.abi8532