Critical Roles of the Pentose Phosphate Pathway and GLN3 in Isobutanol-Specific Tolerance in Yeast

Kouichi Kuroda, Sarah K. Hammer, Yukio Watanabe, José Montaño López, Gerald R. Fink, Gregory Stephanopoulos, Mitsuyoshi Ueda, José L. Avalos

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

This study provides insights into the yeast response to isobutanol and mechanisms underlying specific toxicity and tolerance to isobutanol. Deletion of GLN3 markedly increases yeast tolerance specifically to branched-chain alcohols and isobutanol production. Deletion of GLN3 evades the native nitrogen starvation response induced by isobutanol, enhancing isobutanol tolerance. These findings illustrate how adaptive mechanisms to tolerate stress can lead to toxicity in chemical production and provide a promising strategy to boost production by genetically disrupting such mechanisms.

Original languageEnglish (US)
Pages (from-to)534-547.e5
JournalCell Systems
Volume9
Issue number6
DOIs
StatePublished - Dec 18 2019

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Keywords

  • GCN4
  • GLN3
  • Saccharomyces cerevisiae
  • TOR
  • alcohol tolerance
  • amino acid biosynthesis
  • genome-wide screen
  • isobutanol
  • nitrogen catabolite repression
  • pentose phosphate pathway

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