“…Typically, the rate of cellulose hydrolysis by enzymes decreases rapidly with conversion, leading to decreased yields, long processing times, and high enzyme usage; and the rate of soluble sugar formation per amount of adsorbed enzyme dramatically declines as hydrolysis progresses (Nutor and Converse, 1991;Wang and Converse, 1992). Many hypotheses have been presented to explain this observation, including thermal instability of cellulases (Caminal et al, 1985;Converse et al, 1988;Eriksson et al, 2002a,b;Gonzalez et al, 1989), hydrolysis product inhibition (Eriksson et al, 2002b;Gan et al, 2003;Gusakov and Sinitsyn, 1992;Holtzapple et al, 1990;Kadam et al, 2002;Todorovic et al, 1987), cellulase inactivation (Converse et al, 1988;Gusakov and Sinitsyn, 1992;Gusakov et al, 1987;Mukataka et al, 1983;Ooshima et al, 1990;Reese, 1982;Sinitsyn et al, 1986;Sutcliffe and Saddler, 1986), enzyme slowing down/stopping (Desai and Converse, 1997), substrate transformation into a less digestible form (Zhang et al, 1999), and/or the heterogeneous structure of the substrate (Nidetzky and Steiner, 1993;Zhang et al, 1999). ''Restart'' experiments have been used to identify factors that control the rate of cellulose hydrolysis (Desai and Converse, 1997;Gusakov et al, 1985;Nidetzky and Steiner, 1993;Ooshima et al, 1991;Valjamae et al, 1998;Zhang et al, 1999), and some results indicated that the drop in rate for continual hydrolysis of cellulose could be explained by declining substrate reactivity (Zhang et al, 1999).…”