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硫糖在天然产物中的吸收

摘要 : 德克萨斯大学奥斯汀分校联合台湾的一项研究,识别出一个噻唑合成酶同源物BexX,它参与含2- 硫糖的抗生素BE-7585A的生物合成。相关文章发表于2014年5月11日的《Nature》杂志上。

硫原子存在于很多次生代谢物中,但尚不清楚它是怎样被结合到这些天然产物中去的。

Hung-wen Liu及同事识别出一个噻唑合成酶同源物BexX,它参与含2- 硫糖的抗生素BE-7585A的生物合成。BexX通过从半胱氨酸或“钼蝶呤”的生物合成通道获得硫载体蛋白(因为BE-7585A生物合成基因簇不含硫载体基因)来催化6-磷酸葡萄糖向2-硫葡萄糖的转化。

从一级代谢通道劫持硫转移系统来促进一种天然产物的生物合成,代表着一级和次级代谢之间的一个异乎寻常的联系。

原文摘要:

Co-opting sulphur-carrier proteins from primary metabolic pathways for 2-thiosugar biosynthesis

Eita Sasaki, Xuan Zhang, He G. Sun, Mei-Yeh Jade Lu, Tsung-lin Liu, Albert Ou, Jeng-yi Li,Yu-hsiang Chen, Steven E. Ealick & Hung-wen Liu

Sulphur is an essential element for life and is ubiquitous in living systems. Yet how the sulphur atom is incorporated into many sulphur-containing secondary metabolites is poorly understood. For bond formation between carbon and sulphur in primary metabolites, the major ionic sulphur sources are the persulphide and thiocarboxylate groups on sulphur-carrier (donor) proteins. Each group is post-translationally generated through the action of a specific activating enzyme. In all reported bacterial cases, the gene encoding the enzyme that catalyses the carbon–sulphur bond formation reaction and that encoding the cognate sulphur-carrier protein exist in the same gene cluster. To study the production of the 2-thiosugar moiety in BE-7585A, an antibiotic from Amycolatopsis orientalis, we identified a putative 2-thioglucose synthase, BexX, whose protein sequence and mode of action seem similar to those of ThiG, the enzyme that catalyses thiazole formation in thiamine biosynthesis. However, no gene encoding a sulphur-carrier protein could be located in the BE-7585A cluster. Subsequent genome sequencing uncovered a few genes encoding sulphur-carrier proteins that are probably involved in the biosynthesis of primary metabolites but only one activating enzyme gene in the A. orientalis genome. Further experiments showed that this activating enzyme can adenylate each of these sulphur-carrier proteins and probably also catalyses the subsequent thiolation, through its rhodanese domain. A proper combination of these sulphur-delivery systems is effective for BexX-catalysed 2-thioglucose production. The ability of BexX to selectively distinguish sulphur-carrier proteins is given a structural basis using X-ray crystallography. This study is, to our knowledge, the first complete characterization of thiosugar formation in nature and also demonstrates the receptor promiscuity of the A. orientalis sulphur-delivery system. Our results also show that co-opting the sulphur-delivery machinery of primary metabolism for the biosynthesis of sulphur-containing natural products is probably a general strategy found in nature.

对应Nature杂志: 2014年6月19日Nature杂志精选

来源: Nature中文 浏览次数:35

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