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Title: Strategies to reduce end-product inhibition in family 48 glycoside hydrolases

Family 48 cellobiohydrolases are some of the most abundant glycoside hydrolases in nature. They are able to degrade cellulosic biomass and therefore serve as good enzyme candidates for biofuel production. Family 48 cellulases hydrolyze cellulose chains via a processive mechanism, and produce end products composed primarily of cellobiose as well as other cellooligomers (dp ≤ 4). The challenge of utilizing cellulases in biofuel production lies in their extremely slow turnover rate. A factor contributing to the low enzyme activity is suggested to be product binding to enzyme and the resulting performance inhibition. In this study, we quantitatively evaluated the product inhibitory effect of four family 48 glycoside hydrolases using molecular dynamics simulations and product expulsion free-energy calculations. We also suggested a series of single mutants of the four family 48 glycoside hydrolases with theoretically reduced level of product inhibition. As a result, the theoretical calculations provide a guide for future experimental studies designed to produce mutant cellulases with enhanced activity.
 [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] ;  [1] ;  [2] ;  [2] ;  [2]
  1. Cornell Univ., Ithaca, NY (United States)
  2. National Renewable Energy Lab. (NREL), Golden, CO (United States)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 0887-3585
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 84; Journal Issue: 3; Related Information: Proteins: Structure, Function, and Bioinformatics; Journal ID: ISSN 0887-3585
Research Org:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES; glycoside hydrolases; product inhibition; biofuels; cellulose; molecular dynamics