小柯机器人

美国宾夕法尼亚州立大学Squire J. Booker和Amie K. Boal共同合作近期取得重要工作进展，他们最新研究报导了四醚脂质合成酶的发现、结构和作用机制。相关研究成果2022年7月26日在线出版于《自然》杂志上。

在这里，研究人员展示了来自Methanocaldococcus jannaschii的mj0619基因产物，它编码自由基S-腺苷甲硫氨酸酶，负责在大环古菌醇和GDGT膜脂的合成过程中形成联植烷链。 酶的结构显示存在四种金属辅助因子：三个[Fe₄S₄]簇和一个单核红氧还蛋白样铁离子。体外机理研究表明，Csp³-Csp³键的形成发生在完全饱和的古细菌脂质底物上，并且涉及底物碳和[Fe₄S₄]簇之一的硫之间的中间键。他们的结果不仅建立了四醚形成的生物合成途径，而且完善了GDGT在基于GDGT的古气候学指标中的使用。

据介绍，古细菌合成基于类异戊二烯的醚连接膜脂，使其能够承受极端环境条件，例如高温、高盐度和低或高pH值。在一些古细菌中，例如Methanocaldococcus jannaschii，这些脂质通过在一个甘油磷脂内的两个脂质尾部的末端之间形成碳-碳键来进一步修饰，以生成大环古菌醇或在两个末端之间形成两个碳-碳键以产生大环甘油二脂酰甘油四醚（GDGT）。GDGT 包含两条40碳的脂质链（联植烷基链），它们跨越膜的两个小叶，在极端条件下提供增强的稳定性。这些特殊的脂质是如何形成的，几十年来一直困扰着科学家们。该反应需要两个完全惰性的sp³杂化碳中心的偶联，据研究人员所知，这在自然界中尚未观察到。

附：英文原文

Title: Discovery, structure, and mechanism of a tetraether lipid synthase

Author: Lloyd, Cody T., Iwig, David F., Wang, Bo, Cossu, Matteo, Metcalf, William W., Boal, Amie K., Booker, Squire J.

Issue&Volume: 2022-07-26

Abstract: Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, high salinity, and low or high pH values. 1-5 In some archaea, such as Methanocaldococcus jannaschii, these lipids are further modified by forming carbon-carbon bonds between the termini of two lipid tails within one glycerophospholipid to generate the macrocyclic archaeol or forming two carbon-carbon bonds between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). 1,2 GDGT contains two 40-carbon lipid chains (biphytanyl chains) that span both leaflets of the membrane, providing enhanced stability to extreme conditions. How these specialized lipids are formed has puzzled scientists for decades. The reaction necessitates the coupling of two completely inert sp3-hybridized carbon centers, which, to our knowledge, has not been observed in nature. Herein, we show that the gene product of mj0619 from Methanocaldococcus jannaschii, which encodes a radical S-adenosylmethionine enzyme, is responsible for biphytanyl chain formation during synthesis of both the macrocyclic archaeol and GDGT membrane lipids. 6 Structures of the enzyme show the presence of four metallocofactors: three [Fe4S4] clusters and one mononuclear rubredoxin-like iron ion. In vitro mechanistic studies show that Csp3-Csp3 bond formation takes place on fully saturated archaeal lipid substrates and involves an intermediate bond between the substrate carbon and a sulfur of one of the [Fe4S4] clusters. Our results not only establish the biosynthetic route for tetraether formation but improve the use of GDGT in GDGT-based paleoclimatology indices. 7-10.

DOI: 10.1038/s41586-022-05120-2

Source: https://www.nature.com/articles/s41586-022-05120-2

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