## 4 Diversity of Microbial Cellulases  
A large diversity of endocellases and exocellases has been characterized in aerobic and anaerobic bacteria and fungi, protozoa and some unique animal species [12; 26]. Endocellulares and exocellases are further classified into non-complex free cellulases [12; 26] and the complex cellulosomes [26] based upon how these enzymes are associated with their original organisms and what biological mechanisms that these enzymes employ to carry out cellulose degradation. The highest wild-type bacterial free cellulase activity was reported at about 2.5 U/mg protein on Avicel for a GH9 processive endoglucanase originated from _Clostidium phytorementans_[78] and a GH5 bacterial endoglucanase screened from the Buffalo rumen metagenomic library [55]. Directed evolution of this _Clostidium phytorementans_ GH9 processive endoglucanase further enhanced its activity to about 6 U/mg protein on Avicel [79]. The highest fungal free cellulase activities were reported at 9.7 and 29.8 U/mg protein for two exocellases on Avicel and these free cellulaseswere respectively originated from ruminal _Neocallimastix patriciarum_[80] and the White Rot fungus _Irpex lactaeus_[75]. The highest purified cellulose activities were reported at 9.6-14.6 U/mg protein on Avicel from _Clostridium thermocellum_[81]. It is apparent that these abovementioned highest levels of cellulose specific activities reported so far for hydrolyzing crystalline cellulose substrates are still far below the specific activities reported for some of the well-established industrial enzymes such as commercial phytases, hemicellulases and \(\alpha\)-amylases, typically having specific activity ranging from several hundreds to thousands U/mg protein. Thus, it is imperative to continue the research efforts for the discovery and engineering of highly active endocellulares and exocellulases for their various industrial applications. Free cellulases are typically secreted out of their originating organisms or cells and are sloughed into surrounding environments and these enzymes are further divided into mono-modular, possessing only one catalytic domain, bi-modular, having one carbohydrate-binding domain or module (CBD or CBM) and one catalytic domain, and multi-modular, containing one or more CBD and one or more catalytic domains, cellulases [12; 26; 27]. The classic view is that almost all cellulase enzymes that degrade insoluble substrates contain a substrate-binding domain linked to the catalytic domain via a linker peptide [12]. [PERSON] et al. (2013) demonstrated that fusion of a cellulose-binding module enhanced cellulase binding affinity and cellulolytic activity to insoluble cellulosic substrates [82]. However, possessing a CBD in cellulases does not mean that cellulases have high activity on insoluble especially crystalline cellulasic substrates, which is deemed to be an essential property for potential industrial applications. For example, two ruminal GH5 cellulases that were characterized to contain CBD could effectively hydrolyze soluble substrate CMC but did not have activities on the model crystalline cellulosic substrate Avicel [83; 84]. A number of free cellulases that are reported to possess CBD have little or no activities on model crystalline cellulosic substrates as compiled in the Braunschweig Brenda Enzyme Database ([[http://www.brenda-enzyme.org](http://www.brenda-enzyme.org)]([http://www.brenda-enzyme.org](http://www.brenda-enzyme.org))). Alternatively, cellulose substrates as ligands can directly bind to catalytic domains to engage hydrolysis with non-processive and processive cellulases [85]. [PERSON] et al. (2011) [86] and [PERSON] et al. (2013) [87] further demonstrated that cellulases bound to hydrophobic regions in catalytic domain active sites, especially the tryptophan residues in processive cellulases.