Engineered yeast tolerance enables efficient production from toxified lignocellulosic feedstocks
Journal article, 2021

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.


Felix H. Lam

Whitehead Institute for Biomedical Research

Massachusetts Institute of Technology (MIT)

Burcu Turanli-Yildiz

Massachusetts Institute of Technology (MIT)

Whitehead Institute for Biomedical Research

Dany Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Michael G. Resch

National Renewable Energy Laboratory

Gerald R. Fink

Whitehead Institute for Biomedical Research

Gregory Stephanopoulos

Massachusetts Institute of Technology (MIT)

Science advances

2375-2548 (eISSN)

Vol. 7 26 eabf7613

Subject Categories

Chemical Process Engineering


Biocatalysis and Enzyme Technology





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