(Bio)Catalyst Design for Lignin Deconstruction and Utilization
Lignin is a heterogeneous, alkyl-aromatic polymer found in plant cell walls for defense, structure, and water transport. Lignin is composed of three types of phenyl propanoid monomer units, linked together by various carbon-carbon and carbon-oxygen bonds. An illustration of lignin is shown below. In current selective routes for biomass utilization, lignin is typically burned for heat and power. However, the energy and aromatic content in lignin makes it an attractive target for biological and catalytic conversion to usable intermediates for fuels and chemicals. As such, our group is actively designing and developing chemical and biological catalysts to deconstruct and upgrade lignin to value-added molecules.
We use a combined theoretical and experimental approach to understand the most labile bonds in lignin, to design chemical catalysts to cleave those bonds, and to understand how various pretreatment options affect lignin structure and chemistry. The theoretical component of our work utilizes quantum mechanical calculations with transition state theory to understand reaction mechanisms, barrier heights, and rates with various homogeneous and heterogeneous catalysts from the literature and from our own designs.
Experimentally, we have synthesized libraries of model compounds to mimic the most prevalent linkages in lignin, which are used in catalyst screening. We are screening multiple pretreatment and post-treatment methods to isolate lignin in the context of an integrated biorefinery. We are also developing biological approaches to catabolize the heterogeneous slate of aromatics produced in various lignin depolymerization strategies. This "Biological Funneling" concept takes advantage of natural aromatic catabolic pathways to convert lignin-derived aromatics into value-added compounds. To date, we have demonstrated the production of medium-chain-length polyhydroxyalkanoates (mcl-PHAs) via a native organism, Pseudomonas putida. In an engineered strain of the same organism, we have also demonstrated muconic acid production, which is a precursor to many industrial polymers including Nylon-6,6. This research will be used directly in techno-economic models to couple our laboratory-scale work to understanding how lignin utilization will be integrated into next-generation biorefineries.
Cellulase Enzyme Structure-Function Relationships
I am interested in the mechanisms by which processive cellulase enzymes interact with and degrade crystalline cellulose with an aim to design enhanced cellulase systems as well as biomimetic chemical catalysts for overcoming biomass recalcitrance. To date, my research efforts have focused on the Family 7 cellobiohydrolase (Cel7A) from Trichoderma reesei, which is one of the primary components of industrial enzyme cocktails for biomass conversion.
We study the individual sub-domains of this particular enzyme. To date, we have predicted that the Cel7A CBM exhibits 1 nanometer potential energy wells along the hydrophobic cellulose surface, we have shown that the linker is an intrinsically disordered protein with and without glycosylation, and with Tina Jeoh at UC Davis we demonstrated that changes to glycosylation affects the enzyme activity substantially. We have additional computational and experimental studies in progress on this enzyme, and related cellulase and hemicellulase enzymes from fungal and bacterial systems. Our recent review articles in Current Opinion in Biotechnology and Annual Reviews in Chemical and Biomolecular Engineering describe the capabilities and limitations of molecular and coarse-grained simulation approaches to aid experimental studies to understand structure-function relationships in carbohydrate-active enzymes.
The simulation tools we used for this research include Transition Path Sampling, Aimless Shooting and Likelihood Maximization, Replica-Exchange Molecular Dynamics, and a suite of free energy methods such as MD Umbrella Sampling, Equilibrium Path Sampling, and the Finite Temperature String Method. Our group primarily uses CHARMM, Amber, LAMMPS, and NAMD, and two staff members at NREL are involved in the development of the first three codes mentioned (namely, Mike Crowley and Antti-Pekka Hynninen).
Biopolymer Material Properties
Cellulose and chitin are two of the most abundant biological materials on Earth, and both polymers form recalcitrant, crystalline matrices for defense and structure. Enzymes, such as the Cel7A cellulase shown above, have evolved to deconstruct cellulose and chitin to soluble carbohydrates, but because both polymers form crystalline bundles in nature, enzymes must conduct work to decrystallize individual polymers from crystal surfaces. The work that enzymes must conduct is a function of the particular crystal form, or polymorph, of the polymer of interest (cellulose and chitin both have multiple crystal forms), the location of the chain on the crystal surface, and the degree of crystallinity in the substrate. We have used free energy methods to calculate the amount of work that cellulases must conduct to decrystallize cellulose as a function of cellulose polymorph and location of chains on crystal surfaces, as shown below.
We also examined decrystallization of cello-oligomers on the surface of cellulose Iβ. Overall, this body of work has shown that inter-sheet interactions in cellulose dominate the work that enzymes must conduct at short oligomer lengths, and that intra-sheet hydrogen bonds begin to contribute substantially to decrystallization free energy at longer oligomer lengths. We have also shown that the decrystallization work for cellulose II and IIII chains, which are produced via some ionic liquid and ammonia pretreatment strategies respectively, is substantially lower than that for equivalent chains in cellulose I, the latter which is found in plant cell walls.
I also recently extended this work to decrystallization of polymer chains from the hydrophobic face of α-chitin. We showed that the inter-sheet hydrogen bonds present in α-chitin are responsible for much of the work that chitinases must conduct to deconstruct chitin. We are currently extending this work to β-chitin, which is a popular substrate for examining chitinase activity.
Nucleation of Model and Natural Systems
I am also interested in quantitatively describing the mechanisms by which systems self-assemble into ordered phases from disordered phases with molecular simulation. We recently examined the reaction coordinate for nucleation in a common model system, the Lennard-Jones fluid, and verified the first accurate scalar reaction coordinate for nucleation in this system.
In collaboration with faculty from the Center for Hydrate Research at the Colorado School of Mines, we are examining the mechanisms by which water can structure around small molecules to nucleate and grow into crystalline phases, called clathrate hydrates. Clathrate hydrates are a potentially important energy source and route for carbon sequestration, and thus understanding how they form at the molecular level is of paramount importance for energy and climate security.
MIT David H. Koch School of Chemical Engineering Practice at NREL
I am also involved with deployment of the MIT Practice School within the National Bioenergy Center (NBC) at NREL. As of 2014, we have had five stations of the David H. Koch School of Chemical Engineering Practice at MIT working on a variety of projects at NREL in the biochemical, thermochemical, and algal conversion platforms. Several peer-reviewed manuscripts resulting from these efforts are in preparation currently, and multiple presentations have been given at national conferences based on their work.
Ph.D., Chemical Engineering, Massachusetts Institute of Technology, 2007
M.S., Chemical Engineering Practice, Massachusetts Institute of Technology, 2004
B.S., Chemical Engineering, Oklahoma State University, 2002
Senior Engineer, NREL, NBC, 2011–present
Research Assistant Professor, Department of Chemical Engineering, Colorado School of Mines, 2010–present
Affiliate, Renewable and Sustainable Energy Institute, University of Colorado at Boulder, 2010–present
Staff Engineer, NREL, NBC, 2008–2011
Station Director, Massachusetts Institute of Technology, David H. Koch School of Chemical Engineering Practice, 2007
Lecturer, Massachusetts Institute of Technology, Singapore-MIT Alliance, 2005
"Renewable Unsaturated Polyesters from Muconic Acid," ACS Sustainable Chem. Eng. (2016)
"Gradient Elution Moving Boundary Electrophoresis Enables Rapid Analysis of Acids in Complex Biomass-Derived Streams," ACS Sustainable Chem. Eng. (In Press)
"Reductive Catalytic Fractionation of Corn Stover Lignin," ACS Sustainable Chem. Eng. (In Press)
"Aqueous Stream Characterization from Biomass Fast Pyrolysis and Catalytic Fast Pyrolysis," ACS Sustainable Chem. Eng. (In Press)
"Lignin Depolymerization by Fungal Secretomes and a Microbial Sink," Green Chem. (In Press)
"Coupling and Reactions of 5-Hydroxyconiferyl Alcohol in Lignin Formation," J. Ag. Food Chem. (2016)
"Radical Nature of C-Lignin," ACS Sust. Chem. Eng. (In Press)
"Quantification of Acidic Compounds in Complex Biomass-Derived Streams," Green Chem. (2016)
"Succinic Acid Production from Lignocellulosic Hydrolysate by Basfia succiniciproducens," Biores. Tech. (2016)
"The Techno-Economic Basis for Coproduct Manufacturing To Enable Hydrocarbon Fuel Production from Lignocellulosic Biomass," ACS Sust. Chem. Eng. (2016)
"Enhancing muconic acid production from glucose or lignin via increased protocatechuate decarboxylase activity," Metab. Eng. Comm. (2016)
"Furan Production from Glycoaldehyde over HZSM-5," ACS Sust. Chem. Eng. (2016)
"Biochemical and Structural Characterizations of Two Dictyostelium Cellobiohydrolases from the Amoebozoa Kingdom Reveal a High Level of Conservation between Distant Phylogenetic Trees of Life," Appl. Env. Microbiol. (2016)
"Opportunities and Challenges in Biological Lignin Valorization," Curr. Opin. Biotech. (2016)
"Aromatic-Mediated Carbohydrate Recognition in Processive Serratia marcescens Chitinases," J. Phys. Chem. B. (2016)
"Conversion of levoglucosan and cellobiosan by Pseudomonas putida KT2440," Metab. Eng. Comm. (2016)
"Lignin Depolymerization with Nitrate-Intercalated Hydrotalcite Catalysts," ACS Catalysis (2016)
"Base-Catalyzed Depolymerization of Biorefinery Lignins," ACS Sust. Chem. Eng. (2016)
"Electronic Coupling through Natural Amino Acids," J. Chem. Phys. (2015)
"Glycosylation of Cellulases: Engineering Better Enzymes for Biofuels ," In Advances in Carbohydrate Chemistry and Biochemistry (2015)
"Lignocellulose Degradation Mechanisms Across the Tree of Life," Curr. Opin. Chem. Biol. (2015)
"Carbocation Stability in H-ZSM5 at High Temperature," J. Phys. Chem. A. (2015)
"Continuous Succinic Acid Production by Actinobacillus succinogenes on xylose-enriched Hydrolysate," Biotech. Biofuels (2015)
"Alkaline Pretreatment of Switchgrass," ACS Sustainable Chem. Eng. (2015)
"Acidolysis of α-O-4 aryl-ether bonds in lignin model compounds: A modeling and experimental study," ACS Sustainable Chem. Eng. (2015)
"Ethanol dehydration in HZSM-5 studied by density functional theory: Evidence for a concerted process," J. Phys. Chem. A. (2015)
"Fungal Cellulases," Chem. Rev. (2015)
"Aromatic catabolic pathway selection for optimal production of pyruvate and lactate from lignin," Metabolic Eng. (2015)
"Nucleation rate analysis of methane hydrate from molecular dynamics simulations," Faraday Discussions (2015)
"Adipic acid production from lignin," Energy Env. Sci (2015)
"Reaction Coordinate of Incipient Methane Clathrate Hydrate Nucleation," AJ. Phys. Chem. B. (2014)
"Lignin Valorization: Improving Lignin Processing in the Biorefinery," Science (2014)
"Evaluation of clean fractionation pretreatment for the production of renewable fuels and chemicals from corn stover," ACS Sustainable Chem. Eng. (2014)
"The alpha-bet(a) of glucose pyrolysis: computational and experimental investigations of 5-hydroxymethylfurfural and levoglucosan formation reveal implications for cellulose pyrolysis" ACS Sustainable Chem. Eng. (2014)
"Alkaline pretreatment of corn stover: Bench-scale fractionation and stream characterization," ACS Sustainable Chem. Eng. (2014)
"Two-component order parameter for quantifying clathrate hydrate nucleation and growth," J. Chem. Phys. (2014)
"Crystal structure of glycoside hydrolase family 127 β-l-arabinofuranosidase from Bifidobacterium longum," Biochem. Biophys. Res. Comm. (2014)
"Charge engineering of cellulases improves ionic liquid tolerance and reduces lignin inhibition," Biotech. Bioeng. (2014)
"How sugars pucker: Electronic structure calculations map the kinetic landscape of five biologically paramount monosaccharides and their implications for enzymatic catalysis," J. Amer. Chem. Soc. (2014)
"Towards a molecular-level theory of carbohydrate processivity in glycoside hydrolases," Curr. Opin. Biotech. (2014)
"Sodium Ion Interactions with Aqueous Glucose: Insights from Quantum Mechanics, Molecular Dynamics, and Experiment," J. Phys. Chem. B., Featured on cover. (2014)
"Lignin Depolymerisation by Nickel Supported Layered-Double Hydroxide Catalysts," Green Chem. (2014)
"A Perspective on Oxygenated Species in the Refinery Integration of Pyrolysis Oil," Green Chem. (2014)
"The Complete Mitochondrial Genome of Limnoria quadripunctata Holthuis (Isopoda: Limnoriidae," Mitochondrial DNA (2014)
"A Mechanistic Investigation of Acid-Catalyzed Cleavage of Aryl-Ether Linkages: Implications for Lignin Depolymerization in Acidic Environments," ACS Sustainable Chem. Eng. (2014)
"Glycoside Hydrolase Processivity is Directly Related to Oligosaccharide Binding Free Energy," J. Amer. Chem. Soc. (2013)
"Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbons: Dilute-Acid Prehydrolysis and Enzymatic Hydrolysis Deconstruction of Biomass to Sugars and Biological Conversion of Sugars to Hydrcarbons ," NREL Technical Report (2013)
"Impact of alg3 Gene Deletion on Growth, Development, Pigment Production, Protein Secretion, and Functions of Recombinant Trichoderma reesei Cellobiohydrolases in Aspergillus niger," Fungal Genetics and Biology (2013)
"Product Binding Varies Dramatically between Processive and Nonprocessive Cellulase Enzymes," J. Biol. Chem. (2012)
"Comparison of Cellulose Iβ Simulations with Three Carbohydrate Force Fields," J. Chem. Theory Comput. (2012)
"Harnessing Glycosylation to Improve Cellulase Activity," Curr. Opin. Biotech (2012)
"Computational Investigation of Glycosylation Effects on a Family 1 Carbohydrate-Binding Module," J. Biol. Chem. (2012)
"The Cages, Dynamics, and Structuring of Incipient Methane Clathrate Hydrates," Phys. Chem. Chem. Phys. (2011)
"Computational Study of Bond Dissociation Enthalpies for a Large Range of Native and Modified Lignins." J. Phys. Chem. Lett. (2011)
"Coarse-Grain Model for Glucose, Cellobiose, and Cellotetraose in Water," J. Chem. Theor. Comp. (2011)
"Decrystallization of Oligosaccharides from the Cellulose Iβ Surface with Molecular Simulation," J. Phys. Chem. Lett. (2011)
"Optimizing Nucleus Size Metrics for Liquid–Solid Nucleation from Transition Paths of Near-Nanosecond Duration," J. Phys. Chem. Lett. (2011)
"Examination of the α-Chitin Structure and Decrystallization Thermodynamics at the Nanoscale," J. Phys. Chem. B. (2011)
"Modeling the Self-Assembly of the Cellulosome Enzyme Complex," J. Biol. Chem. (2011)
"High-Temperature Behavior of Cellulose I," J. Phys. Chem. B. (2011)
"Deconstruction of Lignocellulosic Biomass to Fuels and Chemicals," Ann. Rev. Chem. Biomolec. Eng. (2011)
"Applications of Computational Science for Understanding Enzymatic Deconstruction of Cellulose," Curr. Opin. Biotech (2011)
"Chapter 13: New Methods to Find Accurate Reaction Coordinates from Path Sampling," in Computational Modeling in Lignocellulosic Biofuel Production (2010)
"Path Sampling Calculation of Methane Diffusivity in Natural Gas Hydrates from a Water-Vacancy Assisted Mechanism," J. Amer. Chem. Soc. (2008)
"Evidence for a Size Dependent Nucleation Mechanism in Solid State Polymorph Transformations," J. Phys. Chem. B. (2008)
"Extensions to the Likelihood Maximization Approach," J. Chem. Phys. (2007)
"Surface-Mediated Nucleation in the Solid-State Polymorph Transformation of Terephthalic Acid," J. Amer. Chem. Soc. (2007)
View all NREL Publications for Gregg T. Beckham.