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研究发现酵母脂肪酸合酶新调节亚基
2020-03-11 12:59

德国马克斯普朗克生物物理化学研究所Ashwin Chari、Holger Stark等研究人员合作发现酵母脂肪酸合酶(FAS)的一个新调节亚基。相关论文于2020年3月10日在线发表于《细胞》。

研究人员报道了一个2.6兆达尔顿α6-β6酿酒酵母FAS γ亚基的发现,高分辨率结构表明,这一亚基能够稳定旋转的FAS构象并从赤道到轴向重新排列ACP结构域。

γ亚基跨过FAS内腔的长度,阻碍FAS的还原酶活性,通过酮还原酶处的动力学滞后来调节NADPH转换,并抑制烯酰还原酶处的非途径反应。

γ亚基描述了FAS中的功能区室。作为支架,其可用于增加天然FAS中不存在的天然和设计的酶促活性。

据介绍,FAS对代谢至关重要,但对于从可再生资源生产精细化学品和生物燃料也具有生物技术意义。在脂肪酸合成过程中,生长的脂肪酸链被认为是由动态酰基载体蛋白结构域穿梭到几个酶活性位点上的。

附:英文原文

Title: Discovery of a Regulatory Subunit of the Yeast Fatty Acid Synthase

Author: Kashish Singh, Benjamin Graf, Andreas Linden, Viktor Sautner, Henning Urlaub, Kai Tittmann, Holger Stark, Ashwin Chari

Issue&Volume: 2020-03-10

Abstract: Fatty acid synthases (FASs) are central to metabolism but are also of biotechnologicalinterest for the production of fine chemicals and biofuels from renewable resources.During fatty acid synthesis, the growing fatty acid chain is thought to be shuttledby the dynamic acyl carrier protein domain to several enzyme active sites. Here, wereport the discovery of a γ subunit of the 2.6 megadalton α6-β6 S. cerevisiae FAS, which is shown by high-resolution structures to stabilize a rotated FAS conformationand rearrange ACP domains from equatorial to axial positions. The γ subunit spansthe length of the FAS inner cavity, impeding reductase activities of FAS, regulatingNADPH turnover by kinetic hysteresis at the ketoreductase, and suppressing off-pathwayreactions at the enoylreductase. The γ subunit delineates the functional compartmentwithin FAS. As a scaffold, it may be exploited to incorporate natural and designedenzymatic activities that are not present in natural FAS.

DOI: 10.1016/j.cell.2020.02.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30211-7

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/
投稿链接:https://www.editorialmanager.com/cell/default.aspx

本期文章:《细胞》:Online/在线发表

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