Promiscuous activities of heterologous enzymes lead to unintended metabolic rerouting in Saccharomyces cerevisiae engineered to assimilate various sugars from renewable biomass

Eun Ju Yun, Eun Joong Oh, Jing Jing Liu, Sora Yu, Dong Hyun Kim, Suryang Kwak, Kyoung Heon Kim, Yong Su Jin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Understanding the global metabolic network, significantly perturbed upon promiscuous activities of foreign enzymes and different carbon sources, is crucial for systematic optimization of metabolic engineering of yeast Saccharomyces cerevisiae. Here, we studied the effects of promiscuous activities of overexpressed enzymes encoded by foreign genes on rerouting of metabolic fluxes of an engineered yeast capable of assimilating sugars from renewable biomass by profiling intracellular and extracellular metabolites. Results: Unbiased metabolite profiling of the engineered S. cerevisiae strain EJ4 revealed promiscuous enzymatic activities of xylose reductase and xylitol dehydrogenase on galactose and galactitol, respectively, resulting in accumulation of galactitol and tagatose during galactose fermentation. Moreover, during glucose fermentation, a trisaccharide consisting of glucose accumulated outside of the cells probably owing to the promiscuous and transglycosylation activity of β-glucosidase expressed for hydrolyzing cellobiose. Meanwhile, higher accumulation of fatty acids and secondary metabolites was observed during xylose and cellobiose fermentations, respectively. Conclusions: The heterologous enzymes functionally expressed in S. cerevisiae showed promiscuous activities that led to unintended metabolic rerouting in strain EJ4. Such metabolic rerouting could result in a low yield and productivity of a final product due to the formation of unexpected metabolites. Furthermore, the global metabolic network can be significantly regulated by carbon sources, thus yielding different patterns of metabolite production. This metabolomic study can provide useful information for yeast strain improvement and systematic optimization of yeast metabolism to manufacture bio-based products.

Original languageEnglish
Article number140
JournalBiotechnology for Biofuels
Volume11
Issue number1
DOIs
Publication statusPublished - 2018 May 14

Keywords

  • Autophagy
  • Carbon source
  • Metabolite profiling
  • Promiscuous activity
  • Renewable biomass
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology
  • Renewable Energy, Sustainability and the Environment
  • Energy(all)
  • Management, Monitoring, Policy and Law

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