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This study demonstrated the efficiency of Ca(II) and Mg(II) in removing inhibition of enzymatic hydrolysis by lignosulfonate through non-productive adsorption of enzymes. Adding 1 mmol/g cellulose of either metal salt restores approximately 65% of the activity lost when a pure cellulose/cellulase solution is spiked with lignosulfonate. Addition of either Ca(II) or Mg(II) is also effective in counteracting soluble inhibitors of cellulase present in unwashed aspen solid substrate produced by SPORL (sulfite pretreatment to overcome recalcitrance of lignocelluloses). Soluble inhibitors are often removed by thoroughly washing the lignocellulosic solid substrate following pretreatment. It was determined that adding 1 mmol of MgSO(4)/g substrate (oven dry) to the unwashed aspen substrate gave enzymatic substrate digestibility (SED) equivalent to that of washing for a range of enzyme loadings. These results demonstrate that applying divalent metal salts eliminates the need for washing, thereby saving considerable process water and cost for production of chemicals and biofuels from lignocellulose., (Published by Elsevier Ltd.)