摘要
芥子油苷是一类含氮、含硫的次生代谢产物,因其在植物与环境相互关系中重要作用而备受瞩目。芥子油苷合成途径在过去二十多年间已经被研究得十分清楚。为了探索芥子油苷代谢与其他代谢途径及生理活动之间的关联,一方面利用生物信息学技术分析了与芥子油苷合成途径相关的代谢网络,另一方面通过代谢组学和蛋白质组学手段分析了代谢组和蛋白质组对脂肪族芥子油苷代谢紊乱的响应,以此解析与芥子油苷代谢相关的代谢途径。综合两方面的结果来看,芥子油苷合成涉及到植物从整体水平上对代谢途径的协同控制。芥子油苷代谢不仅仅是初生代谢的延伸,其整个代谢途径与细胞内信号以及其他物质代谢途径有着紧密的联系。
我们使用具有庞大数据库和强大计算功能的生物信息学软件(AraNet, GeneMania和ATTED-Ⅱ),分析了与芥子油苷代谢相关的代谢网络,包括与植物防御、次生代谢、氨基酸代谢、转运、激素代谢、蛋白质代谢、核苷酸代谢、碳水化合物代谢、信号转导、翻译、细胞壁、生长发育、脂类代谢相关的诸多生理过程。为了验证该模型,我们一方面通过候选基因突变体的基因芯片数据分析芥子油苷基因的表达差异,另一方面选择候选基因分析了突变体和过量表达植株中芥子油苷变化。这两种验证策略表明,我们使用三种软件分析芥子油苷代谢网络、寻找候选基因的方法是有效可行的。在此基础之上,利用该代谢网络模型,我们可以产生更多高质量的假说,并利用实验加以验证。这种生物信息学构建模型的方法很大程度上提高了科学研究的效率。
我们采用包括超高效液相色谱-飞行时间质谱法和气相色谱与质谱联用的非目标代谢物分析技术,分析了代谢组对脂肪族芥子油苷紊乱的响应,以此更为全面地了解芥子油苷代谢网络。氨基酸、碳水化合物、脂类、辅助因子、核酸、多肽、激素代谢物以及次生代谢物等73种化合物含量显著变化。通过互补型蛋白质组学技术,鉴定了215种差异表达蛋白质。功能类群分析表明,差异蛋白质广泛地参与各类生理活动,如与代谢相关,蛋白质结合因子,能量代谢相关,植物防御相关,蛋白质折叠与降解,运输相关,与环境互作相关,蛋白质合成。
Glucosinolate are group of secondary metabolites containing nitrogen and sulfur. Since its roles in plant-envorinment interactions, a lot of attentions have been paid for its metabolism. Last two decades have seen great progresses in glucosinolate biosynthesis. Nowdays, almost all genes in glucosinolate biosynthesis pathway have been identificated. To undersatand plant molecular connections between glucosinilate metabolism and other metabolism pathways/bioprocesses, we employed bioinformatic tools to analyze molecular network of glucosinolate biosynthesis on one hand. On the other hand, we used metabolimcs and proteimics approaches to inverstigate the metabolome and proteome changes response to perturbation of glucosinolate biosynthesis. The results from two parts show, glucosinolate biosynthesis involves the whole plant metabolism which regulates different metabolism pathways. Glucosinolate metabolism is not only a metabolism pathway which extand from primary metabolism, but is also tightly related to cellular signaling and other metabolism pathways.
Bioinformatic tools (AraNet, GeneMania and ATTED-II)with large database and efficient algorithm were used for analyze the metabolism network related to glucosinolate biosynthesis. Our results show that the metabolism network includes stress and defence, secondary metabolism, amino acid metabolism, transport, hormone metabolism, protein metabolism, nucleotide metabolism, carbohydrate metabolism, signal transduction, translation, cell well, development and lipid metabolism. In order to validate the network, on one hand, microarray data of candidate mutants were used for profile glucosinolate biosynthesis genes expression. On the other hand, candidate genemutant and overexpression plants were used for futher glucosinolate analysis. Validation results showed,using bioinformatic tools for analysis glucosinolate metabolism network is a powerful way to discovery of new candidate genes and connections between glucosinolate pathway and other pathways. Creation of an in silico network of glucosinolate biosynthesis will allow the generation of many testable hypotheses and ultimately enable predicative biology.
Meanwhile, we employed nontargeted metabolite analysis performed by ultrahigh-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry to inverstigate metabolome responsed to glucosinolate perturbation.We were able to identify73metabolites display significant changes in levels, which are clustered into eight functional groups, i.e. amino acids, carbohydrate, lipid, cofactors, nucleotide, peptide, hormone, and secondary metabolites. Two complementary proteomic approaches2D-DIGE and iTRAQ were employed to investigate global protein changes in response to glucosinolate perturbation. Both2D-DIGE and iTRAQ identified215differentially expressed proteins, which were overrepresented into eight groups, i.e. metabolism, protein binding, enery, defense, protein fate, transport, interaction with the environment, and protein synthesis.
With findings from bioinformatic, metabolomic, and proteomics analysis, we draw conclusions:1. amino acids and chloroplast metabolism are higly correlated to glucosinolate metabolism;2. Cross-talk between glucosinolate biosynthesis and hormone metabolism;3. glucosinolate perturbation causes oxidatitve stress;4. glucosinolate metabolism realated to plant transport system.
引文
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