Comparative metabolomics reveals biogenesis of ascarosides, a modular library of small-molecule signals in C. elegans.
Comparative metabolomics reveals biogenesis of ascarosides, a modular library of small-molecule signals in C. elegans.
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比较代谢组学揭示了丙烷剂的生物发生，这是秀丽隐杆线虫中小分子信号的模块化库。
DOI：
10.1021/ja210202y
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发表时间：
2012-01-25
影响因子：
15
通讯作者：
Schroeder, Frank C.
中科院分区：
文献类型：
--
作者：
von Reuss, Stephan H.;Bose, Neelanjan;Srinivasan, Jagan;Yim, Joshua J.;Judkins, Joshua C.;Sternberg, Paul W.;Schroeder, Frank C.
在模式生物秀丽线虫中，一个内源性小分子家族，蛔虫苷，作为发育时间和行为的关键调节因子，作用于保守的信号通路的上游。蛔虫苷是基于双脱氧糖的子囊糖，它与不同长度的类似脂肪酸的侧链相连，这些侧链来自于过氧化体的β氧化。尽管它们对线虫生物学的许多方面都很重要，但对蛔虫苷的结构、生物合成和动态平衡的了解仍然不完整。我们使用基于MS/MS的筛选来描述线虫野生型和突变代谢体中的蛔虫苷，这揭示了蛔虫苷衍生物的结构多样性比以前报道的要大得多。对野生型和一系列过氧体β氧化突变体的代谢产物的比较表明，烯醇型辅酶A水合酶MAOC-1在蛔虫苷的生物合成中起着重要作用，并阐明了另外两种酶Acox-1和DHS-28的功能。我们发现，在过氧化体β氧化之后，蛔虫苷被选择性地衍生为不同生物起源的部分，并且这种修饰可以显著影响生物活性，产生在低Femtomol浓度下活性的信号分子。根据这些结果，蛔虫苷似乎是一个小分子信号的模块化文库，整合了三条主要代谢途径的构建块：碳水化合物代谢、脂肪酸的过氧体β氧化和氨基酸分解代谢。我们的筛查进一步表明，蛔虫苷的生物合成直接受到营养状况的影响，最终产品的排泄具有高度的选择性。
In the model organism Caenorhabditis elegans, a family of endogenous small molecules, the ascarosides, function as key regulators of developmental timing and behavior that act upstream of conserved signaling pathways. The ascarosides are based on the dideoxysugar ascarylose, which is linked to fatty acid-like side chains of varying lengths derived from peroxisomal β-oxidation. Despite their importance for many aspects of C. elegans biology, knowledge of ascaroside structures, biosynthesis, and homeostasis remains incomplete. We used an MS/MS-based screen to profile ascarosides in C. elegans wild type and mutant metabolomes, which revealed a much greater structural diversity of ascaroside derivatives than previously reported. Comparison of the metabolomes from wild type and a series of peroxisomal β-oxidation mutants showed that the enoyl CoA-hydratase MAOC-1 serves an important role in ascaroside biosynthesis and clarified the functions of two other enzymes, ACOX-1 and DHS-28. We show that following peroxisomal β-oxidation the ascarosides are selectively derivatized with moieties of varied biogenetic origin and that such modifications can dramatically affect biological activity, producing signaling molecules active at low femtomolar concentrations. Based on these results the ascarosides appear as a modular library of small molecule signals, integrating building blocks from three major metabolic pathways; carbohydrate metabolism, peroxisomal β-oxidation of fatty acids, and amino acid catabolism. Our screen further demonstrates that ascaroside biosynthesis is directly affected by nutritional status and that excretion of the final products is highly selective.
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影响因子：
3.2
作者：
THORSON, JS;LO, SF;LIU, HW
通讯作者：
LIU, HW
影响因子：
2.9
作者：
Zagoriy, Vyacheslav;Matyash, Vitaliy;Kurzchalia, Teymuras
通讯作者：
Kurzchalia, Teymuras
影响因子：
6.1
作者：
Chung K;Zhan M;Srinivasan J;Sternberg PW;Gong E;Schroeder FC;Lu H
通讯作者：
Lu H
影响因子：
4.8
作者：
Joo, Hyoe-Jin;Kim, Kwang-Youl;Paik, Young-Ki
通讯作者：
Paik, Young-Ki
影响因子：
64.8
作者：
McGrath, Patrick T.;Xu, Yifan;Ailion, Michael;Garrison, Jennifer L.;Butcher, Rebecca A.;Bargmann, Cornelia I.
通讯作者：
Bargmann, Cornelia I.