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Title: Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements

Abstract

The Trichoderma reesei Family 7 cellulase (Cel7A) is a key industrial enzyme in the production of biofuels from lignocellulosic biomass. It is a multi-modular enzyme with a Family 1 carbohydrate-binding module, a flexible O-glycosylated linker, and a large catalytic domain. We have used simulation to elucidate new functions for the 3 sub-domains, which suggests new routes to increase the activity of this central enzyme. These findings include new roles for glycosylation, which we have shown can be used to tune the binding affinity. We have also examined the structures of the catalytically-active complex of Cel7A and its non-processive counterpart, Cel7B, engaged on cellulose, which suggests allosteric mechanisms involved in chain binding when these cellulases are complexed on cellulose. Our computational results also suggest that product inhibition varies significantly between Cel7A and Cel7B, and we offer a molecular-level explanation for this observation. Finally, we discuss simulations of the absolute and relative binding free energy of cellulose ligands and various mutations along the CD tunnel, which will affect processivity and the ability of Cel7A (and related enzymes) to digest cellulose. These results highlight new considerations in protein engineering for processive and non-processive cellulases for production of lignocellulosic biofuels.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Org.:
USDOE Office of Energy Efficiency and Renewable Energy Biomass Program
OSTI Identifier:
1042505
DOE Contract Number:  
AC36-08GO28308
Resource Type:
Conference
Resource Relation:
Conference: American Chemical Society. Abstracts of Papers of the 243rd ACS National Meeting, 25-29 March 2012, San Diego, California; Related Information: Abstract No. BIOT-214
Country of Publication:
United States
Language:
English
Subject:
09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES; AFFINITY; BIOFUELS; BIOMASS; CELLULASE; CELLULOSE; CHAINS; ENZYME ACTIVITY; ENZYMES; FREE ENERGY; MUTATIONS; PRODUCTION; PROTEIN ENGINEERING; SIMULATION; TRICHODERMA VIRIDE; Bioenergy; Chemical and Biosciences

Citation Formats

Beckham, G. T., Payne, C. M., Bu, L., Taylor, C. B., McCabe, C., Chu, J. W., Himmel, M. E., and Crowley, M. F. Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements. United States: N. p., 2012. Web.
Beckham, G. T., Payne, C. M., Bu, L., Taylor, C. B., McCabe, C., Chu, J. W., Himmel, M. E., & Crowley, M. F. Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements. United States.
Beckham, G. T., Payne, C. M., Bu, L., Taylor, C. B., McCabe, C., Chu, J. W., Himmel, M. E., and Crowley, M. F. Sun . "Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements". United States.
@article{osti_1042505,
title = {Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements},
author = {Beckham, G. T. and Payne, C. M. and Bu, L. and Taylor, C. B. and McCabe, C. and Chu, J. W. and Himmel, M. E. and Crowley, M. F.},
abstractNote = {The Trichoderma reesei Family 7 cellulase (Cel7A) is a key industrial enzyme in the production of biofuels from lignocellulosic biomass. It is a multi-modular enzyme with a Family 1 carbohydrate-binding module, a flexible O-glycosylated linker, and a large catalytic domain. We have used simulation to elucidate new functions for the 3 sub-domains, which suggests new routes to increase the activity of this central enzyme. These findings include new roles for glycosylation, which we have shown can be used to tune the binding affinity. We have also examined the structures of the catalytically-active complex of Cel7A and its non-processive counterpart, Cel7B, engaged on cellulose, which suggests allosteric mechanisms involved in chain binding when these cellulases are complexed on cellulose. Our computational results also suggest that product inhibition varies significantly between Cel7A and Cel7B, and we offer a molecular-level explanation for this observation. Finally, we discuss simulations of the absolute and relative binding free energy of cellulose ligands and various mutations along the CD tunnel, which will affect processivity and the ability of Cel7A (and related enzymes) to digest cellulose. These results highlight new considerations in protein engineering for processive and non-processive cellulases for production of lignocellulosic biofuels.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2012},
month = {1}
}

Conference:
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