In this work, the objective is to investigate technical operative strategies such as SHF, SSF and hybrids to obtain maximum theoretical conversion of lignocelluloses to ethanol at industrial relevant conditions e.g. 30 to 40% WIS. The highest conversion yield of cellulose to ethanol using wheat straw as substrate was obtained applying the commercial enzymatic preparation Cellic CTec2. This is one of the new generation products containing the oxidative GH61 enzymes, which is indicated to be the key factor in boosting the enzymatic hydrolysis. Along with results on optimising the hydrolysis and fermentation at high WIS, the work revealed that reasonable amounts of glucose was oxidized into non-fermentable gluconic acid as a result of the C1 oxidation by the GH61 enzyme. The impact of gluconic acid production on fermentation yield and possible effect on the overall conversion by inhibition of the β-glucosidase enzymes will be discussed.