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.
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The RNA-seq raw data are available at the Genome Expression Omnibus website (https://www.ncbi.nlm.nih.gov/geo/) using series number GSE151478. The genome sequence data of the evolved strains used in this article are available at the Sequence Read Archive website (https://www.ncbi.nlm.nih.gov/sra) with the accession number PRJNA636080. All other data that support the findings in this study are available upon reasonable request. All plasmids and strains used in this study can be obtained from the corresponding author under a material transfer agreement. Source data are provided with this paper.
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We thank C. Zhan, Z. Dai, H. Lu, T. Doughty, K. Campbell, R. Yu and L. F.-Y. Chao for helpful discussions. We thank J. Hellgren for the help with the RNA-seq data processing and analysis. We thank X. Chen, Z. Zhu and B. Ji for giving valuable advice on writing the manuscript. We thank X. Chen and L. F.-Y. Chao for help with the final polishing of the manuscript. This research was supported by The Novo Nordisk Foundation (NNF10CC1016517, J.N.), the Knut and Alice Wallenberg Foundation (J.N.), FORMAS (2015-01546, Y.C.), the Swedish Energy Agency (43548-1, J.N.), Carl Tryggers Stiftelse (Y.C.) and Ångpanneföreningens Forskningsstiftelse (Y.C.).
The authors declare no competing interests.
Peer review information Nature Catalysis thanks the anonymous reviewers for their contribution to the peer review of this work.
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Li, X., Wang, Y., Li, G. et al. Metabolic network remodelling enhances yeast’s fitness on xylose using aerobic glycolysis. Nat Catal 4, 783–796 (2021). https://doi.org/10.1038/s41929-021-00670-6