Background

Pichia pastoris is one of the most important cell factories for production of industrial enzymes and heterogenous proteins. The genome-scale metabolic model of high quality is crucial for comprehensive understanding of the P. pastoris metabolism.

Methods

In this paper, we upgraded P. pastoris genome-scale metabolic model based on the combination of latest genome annotations and literatures. Then the performance of the new model was evaluated using the Cobra Toolbox v2.0.

Results

Compared with the recently published model iMT1026, the reaction number in the new model iRY1243 was increased from 2035 to 2407 and the metabolite number was increased from 1018 to 1094. Accordingly, the unique ORF number was increased from 1026 to 1243. To improve the metabolic functions of P. pastoris genome-scale metabolic model, the biosynthesis pathways of vitamins and cofactors were carefully added. iRY1243 showed good performances when predicting the growth capability on most of the reported carbon and nitrogen sources, the metabolic flux distribution with glucose as a sole carbon source, the essential and partially essential genes, and the effects of gene deletion or overexpression on cell growth and S-adenosyl-l-methionine production.

Conclusion

iRY1243 is an upgraded P. pastoris genome-scale metabolic model with significant improvements in the metabolic coverage and prediction ability, and thus it will be a potential platform for further systematic investigation of P. pastoris metabolism.

中文翻译：

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占1243个ORF的巴斯德毕赤酵母基因组规模代谢模型的全面重建和评估。

背景

巴斯德毕赤酵母是生产工业酶和异源蛋白质最重要的细胞工厂之一。高质量的基因组规模代谢模型对于全面了解巴斯德毕赤酵母代谢至关重要。

方法

在本文中，我们基于最新的基因组注释和文献相结合，对巴斯德毕赤酵母基因组规模的代谢模型进行了升级。然后使用Cobra Toolbox v2.0评估了新模型的性能。

结果

与最近发布的型号iMT1026相比，新型号iRY1243中的反应数从2035增加到2407，代谢物数从1018增加到1094。因此，独特的ORF数从1026增加到1243。功能毕赤酵母基因组规模代谢模型，小心加入维生素和辅因子的生物合成途径。当预测大多数报道的碳和氮源的生长能力，以葡萄糖作为唯一碳源的代谢通量分布，必需和部分必需基因以及基因缺失或过表达对细胞生长和生长的影响时，iRY1243表现出良好的性能。S-腺苷-1-蛋氨酸的生产。

结论

iRY1243是一种经过改良的巴斯德毕赤酵母基因组规模的代谢模型，在代谢覆盖率和预测能力方面有显着改善，因此它将成为进一步系统研究巴斯德毕赤酵母代谢的潜在平台。