Cellulosic ethanol production from lignocellulosic biomass offers a sustainable solution for transition from fossil based fuels to renewable alternatives. However, a few long-standing technical challenges remain to be addressed in the development of an economically viable fermentation process from lignocellulose. Such challenges include the needs to improve yeast tolerance to toxic inhibitory compounds and to achieve high fermentation efficiency with minimum detoxification steps after a simple biomass pretreatment. Here we report an in-situ detoxification strategy by PEG exo-protection of an industrial dry yeast (starch-base). The exo-protected yeast cells displayed remarkably boosted vitality with high tolerance to toxic inhibitory compounds, and with largely improved ethanol productivity from crude hydrolysate derived from a pretreated lignocellulose. The PEG chemical exoprotection makes the industrial S. cerevisiae yeast directly applicable for the production of cellulosic ethanol with substantially improved productivity and yield, without of the need to use genetically modified microorganisms.Cellulosic ethanol from lignocellulosic biomass through biological fermentation has been recognized as a sustainable transportation fuel due to the most abundant carbohydrate content of the broadly distributed non-food feedstock 1-3 . Very high gravity (VHG) fermentation, referring to the fermentation of high sugar concentrations, offers the advantages of improved overall ethanol productivity (producing ethanol in 10-15 vol%), reduced capital cost, and reduced energy input compared to processes at normal gravity 4 . This technology represents a major progress toward cost-competitive production of cellulosic ethanol. With lignocellulosic biomass as the feedstock, a pretreatment process is typically necessary to generate monomeric sugars from the polysaccharide components of the biomass for the subsequent fermentation process. However, typical pretreatment processes of lignocellulosic materials inevitably generate degradation compounds, e. g., acetic and formic acids, furfural, and 5-hydroxymethylfurfural (HMF) and phenolic compounds [5][6][7] . The residue of these compounds often exists in fermentation broth and functions as toxic inhibitors [8][9][10] . To achieve fermentable sugars in a high-concentration for VHG fermentation, the biomass loading ratio during pretreatment must be increased to a considerably high level, which typically results in high concentrations of inhibitors in the fermentation broth. These inhibitors often significantly reduce the rates of yeast metabolism and the final ethanol titers in the subsequent fermentation step 11,12 . The detrimental effect of the inhibitors remains one of the major barriers to the development of an economically viable process for cellulosic ethanol production [13][14][15] . To overcome the issues related to the inhibitory compounds in the lignocellulosic hydrolysates, some techniques on detoxifying the hydrolysates by removing the toxic chemical residues have been repo...
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