Decoene Thomas, Peters Gert, De Maeseneire Sofie L, De Mey Marjan
Centre for Synthetic Biology, Ghent University , Coupure links 653, 9000 Ghent, Belgium.
Centre for Industrial Biotechnology and Biocatalysis, Ghent University , Coupure links 653, 9000 Ghent, Belgium.
ACS Synth Biol. 2018 Feb 16;7(2):622-634. doi: 10.1021/acssynbio.7b00366. Epub 2018 Feb 5.
Fine-tuning biosynthetic pathways is crucial for the development of economic feasible microbial cell factories. Therefore, the use of computational models able to predictably design regulatory sequences for pathway engineering proves to be a valuable tool, especially for modifying genes at the translational level. In this study we developed a computational approach for the de novo design of 5'-untranslated regions (5'UTRs) in Saccharomyces cerevisiae with a predictive outcome on translation initiation rate. On the basis of existing data, a partial least-squares (PLS) regression model was trained and showed good performance on predicting protein abundances of an independent test set. This model was further used for the construction of a "yUTR calculator" that can design 5'UTR sequences with a diverse range of desired translation efficiencies. The predictive power of our yUTR calculator was confirmed in vivo by different representative case studies. As such, these results show the great potential of data driven approaches for reliable pathway engineering in S. cerevisiae.
微调生物合成途径对于经济可行的微生物细胞工厂的开发至关重要。因此，使用能够为途径工程可预测地设计调控序列的计算模型被证明是一种有价值的工具，特别是对于在翻译水平上修饰基因。在本研究中，我们开发了一种计算方法，用于从头设计酿酒酵母中的5'-非翻译区（5'UTR），并对翻译起始率产生预测结果。基于现有数据，训练了一个偏最小二乘（PLS）回归模型，该模型在预测独立测试集的蛋白质丰度方面表现良好。该模型进一步用于构建“yUTR计算器”，该计算器可以设计具有各种所需翻译效率的5'UTR序列。我们的yUTR计算器的预测能力在体内通过不同的代表性案例研究得到了证实。因此，这些结果显示了数据驱动方法在酿酒酵母中进行可靠途径工程的巨大潜力。
