Adaptively evolved yeast mutants on galactose show trade-offs in carbon utilization on glucose
Adaptively evolved yeast mutants on galactose show trade-offs in carbon utilization on glucose
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DOI：
10.1016/j.ymben.2013.01.007
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发表时间：
2013-03-01
影响因子：
8.4
通讯作者：
Nielsen, Jens
中科院分区：
文献类型：
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作者：
Hong, Kuk-Ki;Nielsen, Jens
适应性进化为代谢工程提供了许多机会；然而，一些限制仍然存在，因为进化权衡可能会增加获得新特征的附带成本。通过对分子机制的阐明，可以进一步提高适应性进化在菌株发育中的应用。在这项研究中，具有改进半乳糖利用能力的适应性进化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权衡的分子遗传基础。由于半乳糖利用的改善而引起的转录和代谢变化在葡萄糖的生长过程中得以维持。此外，葡萄糖抑制相关基因在两种糖的生长过程中表现出保守的表达模式。在进化突变体中，被鉴定为有利于半乳糖利用的RAS2基因突变与葡萄糖利用的衰减具有显著相关性。这些结果表明，拮抗多效性是观察到的权衡的主要机制，它可能是通过葡萄糖信号的变化来实现的。(c) 2013爱思唯尔公司版权所有。
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. (c) 2013 Elsevier Inc. All rights reserved.