Evolutionary engineering improves tolerance for medium-chain alcohols in Saccharomyces cerevisiae

Stephanie A. Davis López, Douglas Andrew Griffith, Brian Choi, Jamie H.D. Cate, Danielle Tullman-Ercek*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background: Yeast-based chemical production is an environmentally friendly alternative to petroleum-based production or processes that involve harsh chemicals. However, many potential alcohol biofuels, such as n-butanol, isobutanol and n-hexanol, are toxic to production organisms, lowering the efficiency and cost-effectiveness of these processes. We set out to improve the tolerance of Saccharomyces cerevisiae toward these alcohols. Results: We evolved the laboratory strain of S. cerevisiae BY4741 to be more tolerant toward n-hexanol and show that the mutations which confer tolerance occur in proteins of the translation initiation complex. We found that n-hexanol inhibits initiation of translation and evolved mutations in the α subunit of eIF2 and the γ subunit of its guanine exchange factor eIF2B rescue this inhibition. We further demonstrate that translation initiation is affected by other alcohols such as n-pentanol and n-heptanol, and that mutations in the eIF2 and eIF2B complexes greatly improve tolerance to these medium-chain alcohols. Conclusions: We successfully generated S. cerevisiae strains that have improved tolerance toward medium-chain alcohols and have demonstrated that the causative mutations overcome inhibition of translation initiation by these alcohols.

Original languageEnglish (US)
Article number90
JournalBiotechnology for Biofuels
Issue number1
StatePublished - Apr 2 2018


  • Alcohol tolerance
  • Biofuels
  • Medium-chain alcohols
  • Saccharomyces cerevisiae
  • Translation initiation
  • eIF2
  • eIF2B

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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