Genome Scale Metabolic Modeling of the Riboflavin Overproducer Ashbya gossypii
Genome Scale Metabolic Modeling of the Riboflavin Overproducer Ashbya gossypii
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DOI：
10.1002/bit.25167
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发表时间：
2014-06-01
影响因子：
3.8
通讯作者：
Nielsen, Jens
中科院分区：
文献类型：
--
作者：
Ledesma-Amaro, Rodrigo;Kerkhoven, Eduard J.;Nielsen, Jens
棉阿舒囊菌是一种丝状真菌，天然过量产生核黄素或维生素B2。A.植物遗传代谢工程研究进展棉蚜使这种维生素从工业化学合成转向目前的生物技术生产。此外，还发现了A.棉花是一种模式生物，其最小的真核生物基因组之一在遗传学上接近酿酒酵母。因此，它已被用于研究面包酵母的进化方面。本文首次构建了A.棉，iRL 766。生物量的增长，核黄素生产和底物利用率的预测模型进行了验证。基因必要性分析gossypii模式与S.酿酒酵母模型证明了分离两个物种的全基因组复制事件如何导致旁系同源物在所有代谢途径中均匀分布。此外，iRL 766用于整合来自A.棉蚜，比较指数增长核黄素生产阶段。报告代谢物分析和转录调控酶的计算机识别都证明了核黄素生产中β-氧化和乙醛酸循环的重要参与。Biotechnol. Bioeng. 2014;111：1191-1199. (c)2013 Wiley Periodicals，Inc.
Ashbya gossypii is a filamentous fungus that naturally overproduces riboflavin, or vitamin B2. Advances in genetic and metabolic engineering of A. gossypii have permitted the switch from industrial chemical synthesis to the current biotechnological production of this vitamin. Additionally, A. gossypii is a model organism with one of the smallest eukaryote genomes being phylogenetically close to Saccharomyces cerevisiae. It has therefore been used to study evolutionary aspects of bakers' yeast. We here reconstructed the first genome scale metabolic model of A. gossypii, iRL766. The model was validated by biomass growth, riboflavin production and substrate utilization predictions. Gene essentiality analysis of the A. gossypii model in comparison with the S. cerevisiae model demonstrated how the whole-genome duplication event that separates the two species has led to an even spread of paralogs among all metabolic pathways. Additionally, iRL766 was used to integrate transcriptomics data from two different growth stages of A. gossypii, comparing exponential growth to riboflavin production stages. Both reporter metabolite analysis and in silico identification of transcriptionally regulated enzymes demonstrated the important involvement of beta-oxidation and the glyoxylate cycle in riboflavin production. Biotechnol. Bioeng. 2014;111: 1191-1199. (c) 2013 Wiley Periodicals, Inc.