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A coarse-grained model for synergistic action of multiple enzymes on cellulose.

Asztalos A, Daniels M, Sethi A, Shen T, Langan P, Redondo A, Gnanakaran S - Biotechnol Biofuels (2012)

Bottom Line: We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level.Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails.This model constitutes a critical step towards testing hypotheses and understanding approaches for maximizing synergy and substrate properties with a goal of cost effective enzymatic hydrolysis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA. gnana@lanl.gov.

ABSTRACT

Background: Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates.

Results: We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages) and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose.

Conclusions: Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails. This model constitutes a critical step towards testing hypotheses and understanding approaches for maximizing synergy and substrate properties with a goal of cost effective enzymatic hydrolysis.

No MeSH data available.


Related in: MedlinePlus

Flowchart presenting the actions of an endo-cellulase. The actions are: adsorption onto the cellulose surface (ADSORB), breaking hydrogen bonds (BREAK H. Bs.), hydrolyzing the glycosidic bond (CLEAVE Glyc. B.), and desorption from the cellulose (DESORB). Green rectangles denote chemical reactions (events) and orange ellipses denote branching points. Abbreviations: ‘Glyc. B.’ covalent glycosidic bond; ‘H. Bs.’ hydrogen bonds; ‘nrHB’ number of hydrogen bonds present between the monomers covered by the cellulase.
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Figure 2: Flowchart presenting the actions of an endo-cellulase. The actions are: adsorption onto the cellulose surface (ADSORB), breaking hydrogen bonds (BREAK H. Bs.), hydrolyzing the glycosidic bond (CLEAVE Glyc. B.), and desorption from the cellulose (DESORB). Green rectangles denote chemical reactions (events) and orange ellipses denote branching points. Abbreviations: ‘Glyc. B.’ covalent glycosidic bond; ‘H. Bs.’ hydrogen bonds; ‘nrHB’ number of hydrogen bonds present between the monomers covered by the cellulase.

Mentions: Cellulases with endo-activity (referred to as endo-cellulases or simply endo) are modeled through a set of interactions between the cellulose surface and among themselves. A detailed description of the actions of adsorbed endo-cellulases is presented in Figure 2, while Table 2 lists the parameters that determine their overall activity. Additionally, a state parameter is used to specify whether the cellulase is adsorbed to the substrate or is in solution. In the future, we plan to incorporate another state parameter to describe a decrystallization step that “prepares” the substrate for productive binding.


A coarse-grained model for synergistic action of multiple enzymes on cellulose.

Asztalos A, Daniels M, Sethi A, Shen T, Langan P, Redondo A, Gnanakaran S - Biotechnol Biofuels (2012)

Flowchart presenting the actions of an endo-cellulase. The actions are: adsorption onto the cellulose surface (ADSORB), breaking hydrogen bonds (BREAK H. Bs.), hydrolyzing the glycosidic bond (CLEAVE Glyc. B.), and desorption from the cellulose (DESORB). Green rectangles denote chemical reactions (events) and orange ellipses denote branching points. Abbreviations: ‘Glyc. B.’ covalent glycosidic bond; ‘H. Bs.’ hydrogen bonds; ‘nrHB’ number of hydrogen bonds present between the monomers covered by the cellulase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475064&req=5

Figure 2: Flowchart presenting the actions of an endo-cellulase. The actions are: adsorption onto the cellulose surface (ADSORB), breaking hydrogen bonds (BREAK H. Bs.), hydrolyzing the glycosidic bond (CLEAVE Glyc. B.), and desorption from the cellulose (DESORB). Green rectangles denote chemical reactions (events) and orange ellipses denote branching points. Abbreviations: ‘Glyc. B.’ covalent glycosidic bond; ‘H. Bs.’ hydrogen bonds; ‘nrHB’ number of hydrogen bonds present between the monomers covered by the cellulase.
Mentions: Cellulases with endo-activity (referred to as endo-cellulases or simply endo) are modeled through a set of interactions between the cellulose surface and among themselves. A detailed description of the actions of adsorbed endo-cellulases is presented in Figure 2, while Table 2 lists the parameters that determine their overall activity. Additionally, a state parameter is used to specify whether the cellulase is adsorbed to the substrate or is in solution. In the future, we plan to incorporate another state parameter to describe a decrystallization step that “prepares” the substrate for productive binding.

Bottom Line: We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level.Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails.This model constitutes a critical step towards testing hypotheses and understanding approaches for maximizing synergy and substrate properties with a goal of cost effective enzymatic hydrolysis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA. gnana@lanl.gov.

ABSTRACT

Background: Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates.

Results: We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages) and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose.

Conclusions: Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails. This model constitutes a critical step towards testing hypotheses and understanding approaches for maximizing synergy and substrate properties with a goal of cost effective enzymatic hydrolysis.

No MeSH data available.


Related in: MedlinePlus