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Adaptive evolution offers many opportunities in metabolic engineering; however, several constraints still exist as evolutionary trade-offs may impose collateral cost to obtain new traits. The application of adaptive evolution for strains development could be further improved by elucidating the molecular mechanisms. In this study, adaptively evolved yeast mutants with improved galactose utilization ability showed impaired glucose utilization. The molecular genetic basis of this trade-off was investigated using a systems biology approach. Transcriptional and metabolic changes resulting from the improvement of galactose utilization were found maintained during growth on glucose. Moreover, glucose repression related genes showed conserved expression patterns during growth on both sugars. Mutations in the RAS2 gene that were identified as beneficial for galactose utilization in evolved mutants exhibited significant correlation with attenuation of glucose utilization. These results indicate that antagonistic pleiotropy is the dominant mechanism in the observed trade-off, and it is likely realized by changes in glucose signaling. ? 2013 Elsevier Inc.
机译:适应性进化为代谢工程提供了许多机会。然而,由于进化的取舍可能会增加获得新特性的附带成本,因此仍然存在一些限制。通过阐明分子机制,可以进一步改进适应性进化在菌株开发中的应用。在这项研究中,具有改进的半乳糖利用能力的适应性进化的酵母突变体显示葡萄糖利用受损。使用系统生物学方法研究了这种折衷的分子遗传基础。发现在葡萄糖生长期间,由于半乳糖利用的改善而导致的转录和代谢变化得以保持。此外,葡萄糖抑制相关基因在两种糖上的生长过程中均显示出保守的表达模式。 RAS2基因中的突变被认为对进化突变体中的半乳糖利用有益,表现出与葡萄糖利用的衰减显着相关。这些结果表明,拮抗多效性是观察到的折衷的主要机制,很可能是通过葡萄糖信号的变化来实现的。 ? 2013爱思唯尔公司

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