2016年5月17日，國(guó)際期刊《Biotechnology and Bioengineering》上在線發(fā)表了華東理工大學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室、國(guó)家生化工程技術(shù)研究中心（上海）儲(chǔ)炬教授課題組題為”Comprehensive reconstruction and in silico analysis of Aspergillus niger genome-scale metabolic network model that accounts for 1210 ORFs” 的研究論文。博士研究生（現(xiàn)瑞典查爾姆斯大學(xué)Jens Nielsen教授課題組博士后）魯洪中為論文第一作者，儲(chǔ)炬教授為論文通訊作者。相關(guān)研究為與荷蘭DSM集團(tuán)共同開(kāi)展，并且受益于國(guó)家生化工程技術(shù)研究中心（上海）與華大基因的合作項(xiàng)目輻射。
黑曲霉作為一種常見(jiàn)的且最為重要的細(xì)胞工廠，為工業(yè)生物過(guò)程及大宗生物產(chǎn)品提供了重要的發(fā)酵體系，常見(jiàn)的生產(chǎn)產(chǎn)品包括淀粉酶、有機(jī)酸等。而全基因組代謝網(wǎng)絡(luò)模型（GSMM）的建立無(wú)疑為這一重要菌株的機(jī)理研究及合成生物學(xué)研究奠定了基礎(chǔ)。GSMM的構(gòu)建是一項(xiàng)復(fù)雜且繁瑣的工作，需要對(duì)基因測(cè)序后產(chǎn)生的大量數(shù)據(jù)進(jìn)行分析處理，對(duì)開(kāi)放閱讀框架進(jìn)行辨識(shí)，同時(shí)需要準(zhǔn)確定義相關(guān)反應(yīng)中的元素、ATP及還原力守衡。
魯洪中等基于先期的研究成果，在iMA871模型上進(jìn)行優(yōu)化，主要的優(yōu)化方向包括代謝反應(yīng)的元素守衡及基因-蛋白-反應(yīng)相關(guān)性（Gene-Protein-Reaction associations，GPRs），相關(guān)反應(yīng)數(shù)由1380增加至1764，開(kāi)放閱讀框架由871增加至1210。同時(shí)，通過(guò)額外的轉(zhuǎn)錄組學(xué)分析，68%的反應(yīng)與63%的開(kāi)放閱讀框架可以被準(zhǔn)確定義。建立的模型經(jīng)過(guò)了恒化動(dòng)力學(xué)驗(yàn)證及同位素13C代謝流分析驗(yàn)證，保證了新構(gòu)建的iHL1210模型的可靠性。
原文鏈接：
http://onlinelibrary.wiley.com/doi/10.1002/bit.26195/full
DOI: 10.1002/bit.26195
原文摘要：
Aspergillus niger is one of the most important cell factories for industrial enzymes and organic acids production. A comprehensive genome-scale metabolic network model (GSMM) with high quality is crucial for efficient strain improvement and process optimization. The lack of accurate reaction equations and gene-protein-reaction associations (GPRs) in the current best model of A. niger named GSMM iMA871, however, limits its application scope. To overcome these limitations, we updated the A. niger?GSMM by combining the latest genome annotation and literature mining technology. Compared with iMA871, the number of reactions in iHL1210 was increased from 1,380 to 1,764, and the number of unique ORFs from 871 to 1,210. With the aid of our transcriptomics analysis, the existence of 63% ORFs and 68% reactions in iHL1210 can be verified when glucose was used as the only carbon source. Physiological data from chemostat cultivations, 13C-labeled and molecular experiments from the published literature were further used to check the performance of iHL1210. The average correlation coefficients between the predicted fluxes and estimated fluxes from 13C-labeling data were sufficiently high (above 0.89) and the prediction of cell growth on most of the reported carbon and nitrogen sources was consistent. Using the updated genome-scale model, we evaluated gene essentiality on synthetic and yeast extract medium, as well as the effects of NADPH supply on glucoamylase production in A. niger. In summary, the new A. niger GSMM iHL1210 contains significant improvements with respect to the metabolic coverage and prediction performance, which paves the way for systematic metabolic engineering of A. niger.
