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Cellulosomes are large multi-enzyme complexes associated with the extracellular cell surface mechanized to optimize the attachment and degradation of insoluble, crystalline cellulose structures for further, and easier, hydrolysis of its soluble products.

Cellulose, particularly from plant cell walls, is one the largest sources of organic carbon on Earth. However, its insoluble, crystalline structure makes it difficult for single enzyme degradation, and instead utilizes a synergistic module of cooperation from multiple components, both catalytic and noncatalytic.

History of discovery
Prior to the discovery of cellulosomes, the accepted model of cellulose degradation was mainly studied in aerobic microorganisms. Due to the recalcitrant nature of crystalline cellulose, no single enzyme is known to be able to digest it; rather, cellulolysis involves cooperation of multiple catalytic enzymes to break glycan bonds. Nonetheless, the efficiency of these mechanisms is limited by substrate (cellulose) available and that the product of cellobiose hydrolysis is a negative feedback loop. The decomposition of plant matter which is abundant in cellulose thus sparks intrigue into where efficiency is coming from.

In the early 1980s, Raphael Lamed and Ed Bayer met at Tel Aviv University, Israel and commenced their work that led to the discovery of the cellulosome concept. At the time, they weren’t looking for enzymes or cellulosomes at all. They simply sought a ‘cellulose-binding factor’ or ‘CBF’ on the cell surface of the anaerobic thermophilic bacterium, C. thermocellum, which they inferred would account for the observation that the bacterium attaches strongly to the insoluble cellulose substrate prior to its degradation. They employed a then unconventional experimental approach, in which they isolated an adherence-defective mutant of the bacterium and prepared a specific polyclonal antibody for detection of the functional component. Surprisingly, they isolated a very large multi-sub-unit supra-molecular complex, instead of a small protein. A combination of biochemical, biophysical, immun-ochemical and ultra-structural techniques, followed by molecular biological verification, led to the definition and proof of the cellulosome concept. The birth of the discrete, multi-enzyme cellulosome complex was thus documented.

Currently known cellulosome-producing anaerobic bacteria is further elaborated in Cazypedia:


 * Acetivibrio cellulolyticus
 * Bacteroides cellulosolvens
 * Clostridium acetobutylicum
 * Clostridium cellulolyticum
 * Clostridium cellulovorans
 * Clostridium clariflavum
 * Clostridium josui
 * Clostridium papyrosolvens
 * Clostridium thermocellum (treated as model organism in cellulose utilization and also anaerobic degradation)
 * Ruminococcus albus (dockerins identified, cohesins as yet undetected)
 * Ruminococcus flavefaciens

Structure
Although specific domains and protein structure might vary at regions among different cellulolytic microorganisms, the organization and general model of the cellulosomal structure is relatively consistent. Cellulosome structure and function is primarily based on C. thermocellum, however recent advances in crystallography and biotechnology have extended 3D structural knowledge to C. cellulyticum as well.

The general cellulosome structure consists of two major parts: a noncatalytic scaffoldin protein with “cohesion” domains interact with the “dockerin” domain on each of the multiple catalytic enzymes of diverse spectrum, all dedicated to the eventual degradation of crystalline cellulose. These catalytic enzymes include endoglucanases, cellobiohydrolases, xylanases and other degradative enzymes work synergistically to attack heterogeneous, insoluble cellulose substrates. In C. thermocellum, there are 9 cohesin domains on the scaffoldin CipA at which a recent 3D structure study by Carvalho et al has revealed that the cohesion-dockerin interaction (Coh-Doc) is largely due to a hydrophobic interaction between the cohesion domain and the α-helices on the dockerin from serine and threonine residues.

The cellulosome’s structure increases efficiency by keeping necessary cellulolytic enzymes together for efficient passing of intermediate products and synergistic coordination that is needed for cellulose digestion. This is accomplished by the interaction of two complementary classes of module, located on the two separate types of interacting subunits, i.e., a cohesin module on the scaffoldin and a dockerin module on each enzymatic subunit. The high-affinity cohesin-dockerin interaction defines the cellulosome structure. Attachment of the cellulosome to its substrate is mediated by a scaffoldin-borne cellulose-binding module (CBM) that comprises part of the scaffoldin subunit.

Genetics
Although the framework for the cellulosome (scaffoldin and enzymes) is conserved in species exhibiting cellulose degradation from cellulose, there is much genetic diversity in component genes and locations. C. thermocellum has cellulosomal genes scattered across the chromosome with few gene clusters whereas C. cellulyticum contains a large cluster of six noncellulosomal hydrolase genes of which two form an operon. Genes for specific catalases depend on the species' specificity. Nonetheless, studies of gene clusters in several cellulosome containing microorganisms (see History of Discovery Section), has demonstrated two overall similarities:

1.     First two genes are for the conserved components of the cellulosome, or the scaffoldin and GHF48 exoglucanase enzyme.

2.     The overall genome section resembles a catabolic island.

Applications
Cellulose degradation is a major factor in agricultural and industrial waste. As such, exploitation of cellulosomes for higher efficiency conversion of cellulose in industrial and agricultural waste into fuels and feedstock is a currently explored niche. An continual research in cellulosomes has led to the future ideas such as the ‘supercellulosome’, which would be an artificially constructed cellulosome that can convert cellobiose into a noninhibitory glucose, or the ‘heterocellulosome’, in which cellulosomal components can be switched out to optimize cellulose hydrolysis depending on environment, cellulose structure, and availability.

Intelligent application of cellulosome hybrids and chimeric constructs ("nanosomes") of cellulosomal domains should enable better use of cellulosic biomass and may offer a wide range of novel applications.