Nature Catalysis ( IF 37.8 ) Pub Date : 2021-09-16 , DOI: 10.1038/s41929-021-00670-6 Xiaowei Li 1 , Yanyan Wang 1 , Gang Li 1 , Quanli Liu 1, 2 , Rui Pereira 1, 2 , Yun Chen 1, 2 , Jens Nielsen 1, 2, 3, 4, 5
The reprogramming of metabolism in response to switching the carbon source from glucose to non-preferred carbon sources is well-studied for yeast. However, understanding how metabolic networks respond to utilize a non-natural carbon source such as xylose is limited due to the incomplete knowledge of cellular response mechanisms. Here we applied a combination of metabolic engineering, systems biology and adaptive laboratory evolution to gain insights into how yeast can perform a global rewiring of cellular processes to efficiently accompany metabolic transitions. Through metabolic engineering, we substantially enhanced the cell growth on xylose after the growth on glucose. Transcriptome analysis of the engineered strains demonstrated that multiple pathways were involved in the cellular reprogramming. Through genome resequencing of the evolved strains and reverse engineering, we further identified that SWI/SNF chromatin remodelling, osmotic response and aldehyde reductase were responsible for the improved growth. Combined, our analysis showed that glycerol-3-phosphate and xylitol serve as two key metabolites that affect cellular adaptation to growth on xylose.
中文翻译:
代谢网络重塑通过有氧糖酵解增强酵母对木糖的适应性
针对将碳源从葡萄糖转换为非优选碳源的代谢重编程已对酵母进行了充分研究。然而,由于对细胞反应机制的了解不完整,了解代谢网络如何响应利用非天然碳源(如木糖)受到限制。在这里,我们应用了代谢工程、系统生物学和适应性实验室进化的组合,以深入了解酵母如何对细胞过程进行全球重新布线以有效地伴随代谢转变。通过代谢工程,我们在葡萄糖上生长后显着增强了木糖上的细胞生长。工程菌株的转录组分析表明,细胞重编程涉及多种途径。通过进化菌株的基因组重测序和逆向工程,我们进一步确定 SWI/SNF 染色质重塑、渗透反应和醛还原酶是促进生长的原因。综合起来,我们的分析表明 3-磷酸甘油和木糖醇是影响细胞适应木糖生长的两种关键代谢物。