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Title: Insights into cellulase-lignin non-specific binding revealed by computational redesign of the surface of green fluorescent protein

Journal Article · · Biotechnology and Bioengineering
DOI:https://doi.org/10.1002/bit.26201· OSTI ID:1345115
 [1];  [1];  [2];  [3];  [1]
  1. Michigan State Univ., East Lansing, MI (United States)
  2. Michigan State Univ., East Lansing, MI (United States); Rutgers, The State Univ. of New Jersey, Piscataway, NJ (United States)
  3. National Renewable Energy Lab. (NREL), Golden, CO (United States)

Biological-mediated conversion of pretreated lignocellulosic biomass to biofuels and biochemicals is a promising avenue towards energy sustainability. However, a critical impediment to the commercialization of cellulosic biofuel production is the high cost of cellulase enzymes needed to deconstruct biomass into fermentable sugars. One major factor driving cost is cellulase adsorption and inactivation in the presence of lignin, yet we currently have a poor understanding of the protein structure-function relationships driving this adsorption. In this work, we have systematically investigated the role of protein surface potential on lignin adsorption using a model monomeric fluorescent protein. We have designed and experimentally characterized 16 model protein variants spanning the physiological range of net charge (-24 to +16 total charges) and total charge density (0.28 to 0.40 charges per sequence length) typical for natural proteins. Protein designs were expressed, purified, and subjected to in silico and in vitro biophysical measurements to evaluate the relationship between protein surface potential and lignin adsorption properties. The designs were comparable to model fluorescent protein in terms of thermostability and heterologous expression yield, although the majority of the designs unexpectedly formed homodimers. Protein adsorption to lignin was studied at two different temperatures using Quartz Crystal Microbalance with Dissipation Monitoring and a subtractive mass balance assay. We found a weak correlation between protein net charge and protein-binding capacity to lignin. No other single characteristic, including apparent melting temperature and 2nd virial coefficient, showed correlation with lignin binding. Analysis of an unrelated cellulase dataset with mutations localized to a family I carbohydrate-binding module showed a similar correlation between net charge and lignin binding capacity. Altogether, our study provides strategies to identify highly active, low lignin-binding cellulases by either rational design or by computational screening genomic databases.

Research Organization:
National Renewable Energy Laboratory (NREL), Golden, CO (United States)
Sponsoring Organization:
USDOE Office of Energy Efficiency and Renewable Energy (EERE), Sustainable Transportation Office. Bioenergy Technologies Office (BETO)
Grant/Contract Number:
AC36-08GO28308
OSTI ID:
1345115
Report Number(s):
NREL/JA-2700-66896
Journal Information:
Biotechnology and Bioengineering, Vol. 114, Issue 4; ISSN 0006-3592
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 18 works
Citation information provided by
Web of Science

References (45)

Lignin Biosynthesis journal June 2003
Preferential Adsorption and Activity of Monocomponent Cellulases on Lignocellulose Thin Films with Varying Lignin Content journal March 2013
Use of surface active additives in enzymatic hydrolysis of wheat straw lignocellulose journal March 2007
Electrostatics of nanosystems: Application to microtubules and the ribosome journal August 2001
Next-generation ammonia pretreatment enhances cellulosic biofuel production journal January 2016
Mechanism of lignin inhibition of enzymatic biomass deconstruction journal December 2015
Interactions between Cellulolytic Enzymes with Native, Autohydrolysis, and Technical Lignins and the Effect of a Polysorbate Amphiphile in Reducing Nonproductive Binding journal November 2015
Lignin Impact on Fiber Degradation. 3. Reversal of Inhibition of Enzymatic Hydrolysis by Chemical Modification of Lignin and by Additives journal May 1997
Lignin modification improves fermentable sugar yields for biofuel production journal June 2007
Trichoderma reesei cellobiohydrolase II is associated with the outer membrane when overexpressed in Escherichia coli journal September 2011
The Interrelationship between Promoter Strength, Gene Expression, and Growth Rate journal October 2014
Spectral Perturbations of the Aequorea Green-Fluorescent Protein journal June 1982
Partitioning of Lipid-Modified Monomeric GFPs into Membrane Microdomains of Live Cells journal May 2002
Thermofluor-based high-throughput stability optimization of proteins for structural studies journal October 2006
Structural Insights into the Affinity of Cel7A Carbohydrate-binding Module for Lignin journal July 2015
Inhibition of enzymatic hydrolysis by residual lignins from softwood-study of enzyme binding and inactivation on lignin-rich surface journal June 2011
Isolation of Lignin from Finely Divided Wood with Neutral Solvents journal December 1954
Increased enzyme binding to substrate is not necessary for more efficient cellulose hydrolysis journal June 2013
BSA treatment to enhance enzymatic hydrolysis of cellulose in lignin containing substrates journal January 2006
Biomass Recalcitrance: Engineering Plants and Enzymes for Biofuels Production journal February 2007
The economics of current and future biofuels journal May 2009
Improving the enzymatic hydrolysis of dilute acid pretreated wheat straw by metal ion blocking of non-productive cellulase adsorption on lignin journal May 2016
Binding characteristics of Trichoderma reesei cellulases on untreated, ammonia fiber expansion (AFEX), and dilute-acid pretreated lignocellulosic biomass journal April 2011
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations journal July 2004
Viscoelastic properties of adsorbed and cross-linked polypeptide and protein layers at a solid–liquid interface journal August 2008
Engineering the hydrophobic residues of a GH11 xylanase impacts its adsorption onto lignin and its thermostability journal December 2015
Design, construction and characterization of a set of insulated bacterial promoters journal September 2010
Coding-Sequence Determinants of Gene Expression in Escherichia coli journal April 2009
Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules book January 2011
The fate of lignin during hydrothermal pretreatment journal January 2013
PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations journal May 2007
Computational protein design with explicit consideration of surface hydrophobic patches journal December 2011
Supercharging Proteins Can Impart Unusual Resilience journal August 2007
Adsorption of Trichoderma reesei CBH I and EG II and their catalytic domains on steam pretreated softwood and isolated lignin journal January 2004
Mechanism of surfactant effect in enzymatic hydrolysis of lignocellulose journal August 2002
RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite journal June 2011
Evaluating endoglucanase Cel7B-lignin interaction mechanisms and kinetics using quartz crystal microgravimetry: Interaction Kinetics of Cel7B and Lignin journal July 2015
pH-Induced Lignin Surface Modification to Reduce Nonspecific Cellulase Binding and Enhance Enzymatic Saccharification of Lignocelluloses journal March 2013
Lignin triggers irreversible cellulase loss during pretreated lignocellulosic biomass saccharification journal December 2014
Predicting Enzyme Adsorption to Lignin Films by Calculating Enzyme Surface Hydrophobicity journal May 2014
Lignin Biosynthesis and Structure journal May 2010
Charge engineering of cellulases improves ionic liquid tolerance and reduces lignin inhibition: Impact of Charge on Cellulase Activity in ILs journal March 2014
Predicting protein structures with a multiplayer online game journal August 2010
Whole Proteome pI Values Correlate with Subcellular Localizations of Proteins for Organisms within the Three Domains of Life journal April 2001
Enhancing the enzymatic hydrolysis of lignocellulosic biomass by increasing the carboxylic acid content of the associated lignin journal November 2010

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