Department of Physics and Astronomy, University of Georgia, Athens, Georgia, United States of America.
PLoS One. 2011;6(6):e20671. doi: 10.1371/journal.pone.0020671. Epub 2011 Jun 14.
An ensemble of genetic networks that describe how the model fungal system, Neurospora crassa, utilizes quinic acid (QA) as a sole carbon source has been identified previously. A genetic network for QA metabolism involves the genes, qa-1F and qa-1S, that encode a transcriptional activator and repressor, respectively and structural genes, qa-2, qa-3, qa-4, qa-x, and qa-y. By a series of 4 separate and independent, model-guided, microarray experiments a total of 50 genes are identified as QA-responsive and hypothesized to be under QA-1F control and/or the control of a second QA-responsive transcription factor (NCU03643) both in the fungal binuclear Zn(II)2Cys6 cluster family. QA-1F regulation is not sufficient to explain the quantitative variation in expression profiles of the 50 QA-responsive genes. QA-responsive genes include genes with products in 8 mutually connected metabolic pathways with 7 of them one step removed from the tricarboxylic (TCA) Cycle and with 7 of them one step removed from glycolysis: (1) starch and sucrose metabolism; (2) glycolysis/glucanogenesis; (3) TCA Cycle; (4) butanoate metabolism; (5) pyruvate metabolism; (6) aromatic amino acid and QA metabolism; (7) valine, leucine, and isoleucine degradation; and (8) transport of sugars and amino acids. Gene products both in aromatic amino acid and QA metabolism and transport show an immediate response to shift to QA, while genes with products in the remaining 7 metabolic modules generally show a delayed response to shift to QA. The additional QA-responsive cutinase transcription factor-1β (NCU03643) is found to have a delayed response to shift to QA. The series of microarray experiments are used to expand the previously identified genetic network describing the qa gene cluster to include all 50 QA-responsive genes including the second transcription factor (NCU03643). These studies illustrate new methodologies from systems biology to guide model-driven discoveries about a core metabolic network involving carbon and amino acid metabolism in N. crassa.
先前已经鉴定出了一组描述模式真菌 Neurospora crassa 如何利用奎尼酸 (QA) 作为唯一碳源的遗传网络。QA 代谢的遗传网络涉及分别编码转录激活子和阻遏物的基因 qa-1F 和 qa-1S，以及结构基因 qa-2、qa-3、qa-4、qa-x 和 qa-y。通过一系列 4 个独立的、以模型为导向的微阵列实验，共鉴定出 50 个 QA 响应基因，并假设它们受 QA-1F 控制和/或受第二个 QA 响应转录因子 (NCU03643) 的控制，这两个转录因子都属于真菌双核 Zn(II)2Cys6 簇家族。QA-1F 的调控不足以解释 50 个 QA 响应基因表达谱的定量变化。QA 响应基因包括 8 个相互连接的代谢途径中的基因产物，其中 7 个基因与三羧酸 (TCA) 循环相差一步，7 个基因与糖酵解相差一步：(1) 淀粉和蔗糖代谢；(2) 糖酵解/葡聚糖合成；(3) TCA 循环；(4) 丁酸盐代谢；(5) 丙酮酸代谢；(6) 芳香族氨基酸和 QA 代谢；(7) 缬氨酸、亮氨酸和异亮氨酸降解；和 (8) 糖和氨基酸的运输。芳香族氨基酸和 QA 代谢以及运输的基因产物对转向 QA 有立即反应，而在其余 7 个代谢模块中具有产物的基因通常对转向 QA 有延迟反应。发现另外的 QA 响应角质酶转录因子-1β (NCU03643) 对转向 QA 有延迟反应。一系列微阵列实验用于扩展先前鉴定的遗传网络，该网络描述了包括第二个转录因子 (NCU03643) 在内的所有 50 个 QA 响应基因的 qa 基因簇。这些研究说明了系统生物学中的新方法学，可指导关于涉及 N. crassa 碳和氨基酸代谢的核心代谢网络的模型驱动发现。
