Metabolomic "Dark Matter" Dependent on Peroxisomal β-Oxidation in Caenorhabditis elegans.
Metabolomic "Dark Matter" Dependent on Peroxisomal β-Oxidation in Caenorhabditis elegans.
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DOI：
10.1021/jacs.7b11811
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发表时间：
2018-02-28
影响因子：
15
通讯作者：
Schroeder FC
中科院分区：
文献类型：
--
作者：
Artyukhin AB;Zhang YK;Akagi AE;Panda O;Sternberg PW;Schroeder FC
过氧化物酶体β-氧化（Peroxisomal β-oxidation，pβo）是一种高度保守的脂肪代谢途径，参与动植物多种信号分子的生物合成。在秀丽隐杆线虫中，pβo是蛔虫苷生物合成所必需的，蛔虫苷是控制这种模式生物发育、寿命和行为的信号分子。通过对pβo突变体和野生型的比较质谱分析，我们发现C.线虫和卫星模式太平洋原住民有助于数百种以前未知的代谢物的生命阶段特异性生物合成。代谢组的pβ o依赖性部分出乎意料地多样化，例如与核苷和神经递质代谢交叉。pβ o缺陷突变体中pβo的细胞类型特异性恢复进一步揭示了组织之间pβ o依赖性亚代谢组的差异。这些结果表明，脂肪，核苷和其他主要代谢途径的相互作用可以产生结构多样性，让人想起微生物天然产物生物合成中的组合策略。
Peroxisomal β-oxidation (pβo) is a highly conserved fat metabolism pathway involved in the biosynthesis of diverse signaling molecules in animals and plants. In Caenorhabditis elegans, pβo is required for the biosynthesis of the ascarosides, signaling molecules that control development, lifespan, and behavior in this model organism. Via comparative mass spectrometric analysis of pβo mutants and wildtype, we show that pβo in C. elegans and the satellite model P. pacificus contributes to life stage-specific biosynthesis of several hundred previously unknown metabolites. The pβo-dependent portion of the metabolome is unexpectedly diverse, e.g. intersecting with nucleoside and neurotransmitter metabolism. Cell type-specific restoration of pβo in pβo-defective mutants further revealed that pβo-dependent sub-metabolomes differ between tissues. These results suggest that interactions of fat, nucleoside, and other primary metabolism pathways can generate structural diversity reminiscent of that arising from combinatorial strategies in microbial natural product biosynthesis.
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影响因子：
4.6
作者：
Artyukhin AB;Yim JJ;Cheong Cheong M;Avery L
通讯作者：
Avery L
影响因子：
9.8
作者：
Coburn C;Allman E;Mahanti P;Benedetto A;Cabreiro F;Pincus Z;Matthijssens F;Araiz C;Mandel A;Vlachos M;Edwards SA;Fischer G;Davidson A;Pryor RE;Stevens A;Slack FJ;Tavernarakis N;Braeckman BP;Schroeder FC;Nehrke K;Gems D
通讯作者：
Gems D
影响因子：
64.8
作者：
Fu, J;Gaetani, S;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
9.2
作者：
Hsueh, Yen-Ping;Mahanti, Parag;Schroeder, Frank C.;Sternberg, Paul W.
通讯作者：
Sternberg, Paul W.
影响因子：
1.8
作者：
Garg, Neha;Kapono, Clifford A.;Dorrestein, Pieter C.
通讯作者：
Dorrestein, Pieter C.