Engineered Yeast Tolerance Enables Efficient Production from Toxified Lignocellulosic Feedstocks

Felix Lam, Burcu Turanli-Yildiz, Dany Liu, Michael Resch, Gerald Fink, Gregory Stephanopoulos

Research output: Contribution to journalArticlepeer-review

22 Scopus Citations


Lignocellulosic biomass remains unharnessed for the production of renewable fuels and chemicals due to challenges in deconstruction and the toxicity its hydrolysates pose to fermentation microorganisms. Here, we show in Saccharomyces cerevisiae that engineered aldehyde reduction and elevated extracellular potassium and pH are sufficient to enable near-parity production between inhibitor-laden and inhibitor-free feedstocks. By specifically targeting the universal hydrolysate inhibitors, a single strain is enhanced to tolerate a broad diversity of highly toxified genuine feedstocks and consistently achieve industrial-scale titers (cellulosic ethanol of 100 grams per liter when toxified). Furthermore, a functionally orthogonal, lightweight design enables seamless transferability to existing metabolically engineered chassis strains: We endow full, multifeedstock tolerance on a xylose-consuming strain and one producing the biodegradable plastics precursor lactic acid. The demonstration of "drop-in" hydrolysate competence enables the potential of cost-effective, at-scale biomass utilization for cellulosic fuel and nonfuel products alike.

Original languageAmerican English
Article numbereabf7613
Number of pages13
JournalScience Advances
Issue number26
StatePublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.

NREL Publication Number

  • NREL/JA-5100-79618


  • biomass
  • ethanol
  • feedstock variability
  • fermentation
  • yeast


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