近日，美国加州大学教授程亦凡及其团队研究出人脂肪酸合酶在浓缩循环中的结构动力学。这一研究成果于2025年2月20日发表在国际顶尖学术期刊《自然》上。

在HEK293中标记和纯化内源性FASN用于单粒子低温电镜研究的策略，该课题组表征了内源性人FASN的结构动力学。小组捕获了各种功能亚态在冷凝循环中的构象快照，并开发了一种程序来分析FASN在其冷凝和修饰翼之间不同方向的颗粒分布景观。总之，课题组揭示了FASN函数在冷凝循环中不需要在其两个主要功能域之间进行大的旋转运动，并且两个单体在冷凝循环中进行的催化反应是不同步的。他们的数据提供了脂肪酸合成冷凝循环过程中FASN动态的新复合视图。

研究人员表示，长链脂肪酸是人体脂肪的组成部分。在哺乳动物中，脂肪酸合成酶（FASN）包含多个酶结构域，催化从头合成脂肪酸所需的所有化学反应。虽然这些酶结构域进行的化学反应已经很清楚，但具有开放结构的二聚体FASN如何连续催化这些反应以合成完整的脂肪酸仍然是未知的。

附：英文原文

Title: Structural dynamics of human fatty acid synthase in the condensing cycle

Author: Choi, Wooyoung, Li, Chengmin, Chen, Yifei, Wang, Yongqiang, Cheng, Yifan

Issue&Volume: 2025-02-20

Abstract: Long chain fatty acids are the building blocks of fat in human bodies. In mammals, fatty acid synthase (FASN) contains multiple enzymatic domains to catalyze all chemical reactions needed for de novo fatty acid synthesis1. While the chemical reactions carried out by these enzymatic domains are well defined, how the dimeric FASN with an open architecture continuously catalyzes such reactions to synthesize a complete fatty acid remains elusive. Here, using a strategy of tagging and purifying endogenous FASN in HEK293 for single particle cryogenic electron microscopy studies, we characterized the structural dynamics of endogenous human FASN. We captured the conformational snapshots of various functional substates in the condensing cycle and developed a procedure to analyze particle distribution landscape of FASN with different orientations between its condensing and modifying wings. Together, we reveal that FASN function does not require large rotational motion between its two major functional domains during the condensing cycle, and that the catalytic reactions in condensing cycle carried out by two monomers are unsynchronized. Our data thus provide a new composite view of FASN dynamics during the fatty acid synthesis condensing cycle.

DOI: 10.1038/s41586-025-08782-w

Source: https://www.nature.com/articles/s41586-025-08782-w