Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids

Abstract

Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources to a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis, in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e., binding selectivity). We demonstrate this approach by identifying medium-chain (C8–C12) acyl-ACP thioesterases through structure-guided mutagenesis. Medium-chain fatty acids, which are products of thioesterase-catalyzed hydrolysis, are limited in natural abundance, compared to long-chain fatty acids; the limited supply leads to high costs of C6–C10 oleochemicals such as fatty alcohols, amines, and esters. Here, we applied computational tools to tune substrate binding of the highly active ‘TesA thioesterase in Escherichia coli. We used the IPRO algorithm to design thioesterase variants with enhanced C12 or C8 specificity, while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified 3 variants with enhanced production of dodecanoic acid (C12) and 27 variants with enhancedmore » production of octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A comparably sized library created by random mutagenesis failed to identify promising mutants. The chain length-preference of ‘TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of ‘TesA variants suggest that hydrophobic forces govern ‘TesA substrate specificity. Finally, we expect the design rules that we uncovered and the thioesterase variants that we identified will be useful to metabolic engineering projects aimed at sustainable production of medium-chain-length oleochemicals.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [2];  [1];  [2];  [2];  [3];  [2]; ORCiD logo [1]
+ Show Author Affiliations
  1. Pennsylvania State Univ., University Park, PA (United States). Dept. of Chemical Engineering
  2. Univ. of Wisconsin, Madison, WI (United States). Dept. of Chemical and Biological Engineering
  3. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biochemistry
Publication Date:
Research Org.:
Pennsylvania State Univ., University Park, PA (United States)
Sponsoring Org.:
USDOE Advanced Research Projects Agency - Energy (ARPA-E); National Institutes of Health (NIH)
OSTI Identifier:
1408279
Grant/Contract Number:  
AR0000432; GM115921; GM008505
Resource Type:
Accepted Manuscript
Journal Name:
ACS Catalysis
Additional Journal Information:
Journal Volume: 7; Journal Issue: 6; Journal ID: ISSN 2155-5435
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Dodecanoic acid; fatty acid; IPRO; molecular dynamics; octanoic acid; redesign; thioesterase; ‘TesA

Citation Formats

Grisewood, Matthew J., Hernández-Lozada, Néstor J., Thoden, James B., Gifford, Nathanael P., Mendez-Perez, Daniel, Schoenberger, Haley A., Allan, Matthew F., Floy, Martha E., Lai, Rung-Yi, Holden, Hazel M., Pfleger, Brian F., and Maranas, Costas D. Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids. United States: N. p., 2017. Web. doi:10.1021/acscatal.7b00408.
Copy to clipboard
Grisewood, Matthew J., Hernández-Lozada, Néstor J., Thoden, James B., Gifford, Nathanael P., Mendez-Perez, Daniel, Schoenberger, Haley A., Allan, Matthew F., Floy, Martha E., Lai, Rung-Yi, Holden, Hazel M., Pfleger, Brian F., & Maranas, Costas D. Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids. United States. https://doi.org/10.1021/acscatal.7b00408
Copy to clipboard
Grisewood, Matthew J., Hernández-Lozada, Néstor J., Thoden, James B., Gifford, Nathanael P., Mendez-Perez, Daniel, Schoenberger, Haley A., Allan, Matthew F., Floy, Martha E., Lai, Rung-Yi, Holden, Hazel M., Pfleger, Brian F., and Maranas, Costas D. Thu . "Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids". United States. https://doi.org/10.1021/acscatal.7b00408. https://www.osti.gov/servlets/purl/1408279.
Copy to clipboard
@article{osti_1408279,
title = {Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids},
author = {Grisewood, Matthew J. and Hernández-Lozada, Néstor J. and Thoden, James B. and Gifford, Nathanael P. and Mendez-Perez, Daniel and Schoenberger, Haley A. and Allan, Matthew F. and Floy, Martha E. and Lai, Rung-Yi and Holden, Hazel M. and Pfleger, Brian F. and Maranas, Costas D.},
abstractNote = {Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources to a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis, in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e., binding selectivity). We demonstrate this approach by identifying medium-chain (C8–C12) acyl-ACP thioesterases through structure-guided mutagenesis. Medium-chain fatty acids, which are products of thioesterase-catalyzed hydrolysis, are limited in natural abundance, compared to long-chain fatty acids; the limited supply leads to high costs of C6–C10 oleochemicals such as fatty alcohols, amines, and esters. Here, we applied computational tools to tune substrate binding of the highly active ‘TesA thioesterase in Escherichia coli. We used the IPRO algorithm to design thioesterase variants with enhanced C12 or C8 specificity, while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified 3 variants with enhanced production of dodecanoic acid (C12) and 27 variants with enhanced production of octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A comparably sized library created by random mutagenesis failed to identify promising mutants. The chain length-preference of ‘TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of ‘TesA variants suggest that hydrophobic forces govern ‘TesA substrate specificity. Finally, we expect the design rules that we uncovered and the thioesterase variants that we identified will be useful to metabolic engineering projects aimed at sustainable production of medium-chain-length oleochemicals.},
doi = {10.1021/acscatal.7b00408},
journal = {ACS Catalysis},
number = 6,
volume = 7,
place = {United States},
year = {Thu Apr 20 00:00:00 EDT 2017},
month = {Thu Apr 20 00:00:00 EDT 2017}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1021/acscatal.7b00408
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 62 works
Citation information provided by
Web of Science

Figures / Tables:

Figure 1 Figure 1: Overview of fatty acid biosynthesis and role of acyl-ACP thioesterases. In each cycle of fatty acid biosynthesis, two carbons are added from a malonyl-ACP (M-ACP) yielding a β-ketoacyl-ACP (Kx-ACP where x is the number of carbons). Three reactions (three vertical arrows) reduce the Kx-ACP to a saturated acyl-ACPmore » (Ax-ACP). In E. coli, A16-ACP and A18-ACP are incorporated into membrane lipids. Thioesterases produce free fatty acids by hydrolyzing the acyl-thioester bond (green inset). Tailoring the specificity of the acyl-ACP thioesterase (‘TesA) dictates free fatty acid and downstream oleochemical chain lengths (red arrows).« less
All figures and tables (33 total)
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes
journal, July 2004

  • Davis, I. W.; Murray, L. W.; Richardson, J. S.
  • Nucleic Acids Research, Vol. 32, Issue Web Server
  • DOI: 10.1093/nar/gkh398

Computational design of Candida boidinii xylose reductase for altered cofactor specificity
journal, October 2009

  • Khoury, George A.; Fazelinia, Hossein; Chin, Jonathan W.
  • Protein Science, Vol. 18, Issue 10
  • DOI: 10.1002/pro.227

A simple physical model for binding energy hot spots in protein-protein complexes
journal, October 2002

  • Kortemme, T.; Baker, D.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 22
  • DOI: 10.1073/pnas.202485799

OptGraft: A computational procedure for transferring a binding site onto an existing protein scaffold
journal, January 2008

  • Fazelinia, Hossein; Cirino, Patrick C.; Maranas, Costas D.
  • Protein Science
  • DOI: 10.1002/pro.2

Metabolic engineering strategies for microbial synthesis of oleochemicals
journal, May 2015

Kemp elimination catalysts by computational enzyme design
journal, March 2008

  • Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M.
  • Nature, Vol. 453, Issue 7192, p. 190-195
  • DOI: 10.1038/nature06879

Structural Studies of Fatty Acyl-(Acyl Carrier Protein) Thioesters Reveal a Hydrophobic Binding Cavity that Can Expand to Fit Longer Substrates
journal, January 2007

  • Roujeinikova, Anna; Simon, William J.; Gilroy, John
  • Journal of Molecular Biology, Vol. 365, Issue 1
  • DOI: 10.1016/j.jmb.2006.09.049

Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997

  • Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
  • DOI: 10.1107/S0907444996012255

An automated decision-tree approach to predicting protein interaction hot spots
journal, June 2007

  • Darnell, Steven J.; Page, David; Mitchell, Julie C.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 68, Issue 4
  • DOI: 10.1002/prot.21474

Engineering fungal de novo fatty acid synthesis for short chain fatty acid production
journal, March 2017

  • Gajewski, Jan; Pavlovic, Renata; Fischer, Manuel
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms14650

Expanded Explorations into the Optimization of an Energy Function for Protein Design
journal, September 2013

  • Huang, Yao-ming; Bystroff, Christopher
  • IEEE/ACM Transactions on Computational Biology and Bioinformatics, Vol. 10, Issue 5
  • DOI: 10.1109/TCBB.2013.113

Quantitative analysis and engineering of fatty acid biosynthesis in E. coli
journal, July 2010

The Iterative Protein Redesign and Optimization (IPRO) suite of programs
journal, December 2014

  • Pantazes, Robert J.; Grisewood, Matthew J.; Li, Tong
  • Journal of Computational Chemistry, Vol. 36, Issue 4
  • DOI: 10.1002/jcc.23796

Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

The coming of age of de novo protein design
journal, September 2016

  • Huang, Po-Ssu; Boyken, Scott E.; Baker, David
  • Nature, Vol. 537, Issue 7620
  • DOI: 10.1038/nature19946

Improvement of free fatty acid production using a mutant acyl-CoA thioesterase I with high specific activity in Escherichia coli
journal, October 2016

Identifying residue-residue clashes in protein hybrids by using a second-order mean-field approach
journal, April 2003

  • Moore, G. L.; Maranas, C. D.
  • Proceedings of the National Academy of Sciences, Vol. 100, Issue 9
  • DOI: 10.1073/pnas.0831190100

Regulation of fatty acid biosynthesis in Escherichia coli.
journal, January 1993

“Designer” Biodiesel: Optimizing Fatty Ester Composition to Improve Fuel Properties †
journal, March 2008

Evolving strategies for enzyme engineering
journal, August 2005

Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis
journal, February 2012

  • Khare, Sagar D.; Kipnis, Yakov; Greisen, Per Jr
  • Nature Chemical Biology, Vol. 8, Issue 3
  • DOI: 10.1038/nchembio.777

Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing
journal, November 2012

  • Vanommeslaeghe, K.; MacKerell, A. D.
  • Journal of Chemical Information and Modeling, Vol. 52, Issue 12
  • DOI: 10.1021/ci300363c

Fuelling the future: microbial engineering for the production of sustainable biofuels
journal, March 2016

  • Liao, James C.; Mi, Luo; Pontrelli, Sammy
  • Nature Reviews Microbiology, Vol. 14, Issue 5
  • DOI: 10.1038/nrmicro.2016.32

CHARMM: The biomolecular simulation program
journal, July 2009

  • Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
  • Journal of Computational Chemistry, Vol. 30, Issue 10
  • DOI: 10.1002/jcc.21287

ROSETTALIGAND: Protein-small molecule docking with full side-chain flexibility
journal, November 2006

  • Meiler, Jens; Baker, David
  • Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3
  • DOI: 10.1002/prot.21086

Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges
journal, November 2012

  • Vanommeslaeghe, K.; Raman, E. Prabhu; MacKerell, A. D.
  • Journal of Chemical Information and Modeling, Vol. 52, Issue 12
  • DOI: 10.1021/ci3003649

Cloning and Expression in Escherichia coli of a Novel Thioesterase from Arabidopsis thaliana Specific for Long-Chain Acyl-Acyl Carrier Proteins
journal, January 1995

  • Dormann, P.; Voelker, T. A.; Ohlrogge, J. B.
  • Archives of Biochemistry and Biophysics, Vol. 316, Issue 1
  • DOI: 10.1006/abbi.1995.1081

Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity
journal, January 2011

  • Jing, Fuyuan; Cantu, David C.; Tvaruzkova, Jarmila
  • BMC Biochemistry, Vol. 12, Issue 1
  • DOI: 10.1186/1471-2091-12-44

Protein building blocks preserved by recombination
journal, June 2002

  • Voigt, Christopher A.; Martinez, Carlos; Wang, Zhen-Gang
  • Nature Structural Biology
  • DOI: 10.1038/nsb805

A process for microbial hydrocarbon synthesis: Overproduction of fatty acids in Escherichia coli and catalytic conversion to alkanes
journal, June 2010

  • Lennen, Rebecca M.; Braden, Drew J.; West, Ryan M.
  • Biotechnology and Bioengineering, Vol. 106, Issue 2, p. 193-202
  • DOI: 10.1002/bit.22660

Identification of hot-spot residues in protein-protein interactions by computational docking
journal, October 2008

Structure-guided SCHEMA recombination of distantly related β-lactamases
journal, November 2006

  • Meyer, Michelle M.; Hochrein, Lisa; Arnold, Frances H.
  • Protein Engineering, Design and Selection, Vol. 19, Issue 12
  • DOI: 10.1093/protein/gzl045

Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter.
journal, July 1995

CDD: NCBI's conserved domain database
journal, November 2014

  • Marchler-Bauer, Aron; Derbyshire, Myra K.; Gonzales, Noreen R.
  • Nucleic Acids Research, Vol. 43, Issue D1
  • DOI: 10.1093/nar/gku1221

The Molecular Architecture of Human N -Acetylgalactosamine Kinase
journal, July 2005

  • Thoden, James B.; Holden, Hazel M.
  • Journal of Biological Chemistry, Vol. 280, Issue 38
  • DOI: 10.1074/jbc.M505730200

Synthesis of customized petroleum-replica fuel molecules by targeted modification of free fatty acid pools in Escherichia coli
journal, April 2013

  • Howard, T. P.; Middelhaufe, S.; Moore, K.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 19
  • DOI: 10.1073/pnas.1215966110

IPRO: An Iterative Computational Protein Library Redesign and Optimization Procedure
journal, June 2006

Theoretical and Computational Protein Design
journal, May 2011

Microbial production of short-chain alkanes
journal, September 2013

Microbial production of fatty acid-derived fuels and chemicals
journal, December 2013

Recent advances in computational protein design
journal, August 2011

  • Pantazes, Robert J.; Grisewood, Matthew J.; Maranas, Costas D.
  • Current Opinion in Structural Biology, Vol. 21, Issue 4
  • DOI: 10.1016/j.sbi.2011.04.005

An exciting but challenging road ahead for computational enzyme design: Computational Enzyme Design
journal, September 2010

Methods for the directed evolution of proteins
journal, June 2015

  • Packer, Michael S.; Liu, David R.
  • Nature Reviews Genetics, Vol. 16, Issue 7
  • DOI: 10.1038/nrg3927

HotSpot Wizard: a web server for identification of hot spots in protein engineering
journal, May 2009

  • Pavelka, A.; Chovancova, E.; Damborsky, J.
  • Nucleic Acids Research, Vol. 37, Issue Web Server
  • DOI: 10.1093/nar/gkp410

“The Plot” Thickens: More Data, More Dimensions, More Uses
book, February 2013

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Using a residue clash map to functionally characterize protein recombination hybrids
journal, December 2003

  • Saraf, M. C.; Maranas, C. D.
  • Protein Engineering Design and Selection, Vol. 16, Issue 12
  • DOI: 10.1093/protein/gzg129

Computational structure-based redesign of enzyme activity
journal, February 2009

  • Chen, C. -Y.; Georgiev, I.; Anderson, A. C.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 10
  • DOI: 10.1073/pnas.0900266106

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

Computational Alanine Scanning of Protein-Protein Interfaces
journal, February 2004

Iterative approach to computational enzyme design
journal, February 2012

  • Privett, H. K.; Kiss, G.; Lee, T. M.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 10
  • DOI: 10.1073/pnas.1118082108

Data mining in bioinformatics using Weka
journal, April 2004

Native protein sequences are close to optimal for their structures
journal, September 2000

  • Kuhlman, B.; Baker, D.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 19
  • DOI: 10.1073/pnas.97.19.10383

Extending Iterative Protein Redesign and Optimization (IPRO) in Protein Library Design for Ligand Specificity
journal, March 2007

Manipulating the Stereoselectivity of Limonene Epoxide Hydrolase by Directed Evolution Based on Iterative Saturation Mutagenesis
journal, November 2010

  • Zheng, Huabao; Reetz, Manfred T.
  • Journal of the American Chemical Society, Vol. 132, Issue 44
  • DOI: 10.1021/ja1067542

Computational protein design of ligand binding and catalysis
journal, December 2013

Microbial production of fatty-acid-derived fuels and chemicals from plant biomass
journal, January 2010

  • Steen, Eric J.; Kang, Yisheng; Bokinsky, Gregory
  • Nature, Vol. 463, Issue 7280, p. 559-562
  • DOI: 10.1038/nature08721

Substrate Specificities of Escherichia coli Thioesterase I/Protease I/Lysophospholipase L 1 Are Governed by Its Switch Loop Movement
journal, January 2005

  • Lo, Yu-Chih; Lin, Su-Chang; Shaw, Jei-Fu
  • Biochemistry, Vol. 44, Issue 6
  • DOI: 10.1021/bi048109x

Computational Design of an α-Gliadin Peptidase
journal, December 2012

  • Gordon, Sydney R.; Stanley, Elizabeth J.; Wolf, Sarah
  • Journal of the American Chemical Society, Vol. 134, Issue 50
  • DOI: 10.1021/ja3094795

Efficient free fatty acid production in Escherichia coli using plant acyl-ACP thioesterases
journal, November 2011

Overproduction of free fatty acids in E. coli: Implications for biodiesel production
journal, November 2008

Protein-DNA binding specificity predictions with structural models
journal, October 2005

De Novo Computational Design of Retro-Aldol Enzymes
journal, March 2008

Computational challenges in combinatorial library design for protein engineering
journal, January 2004

  • Moore, Gregory L.; Maranas, Costas D.
  • AIChE Journal, Vol. 50, Issue 2
  • DOI: 10.1002/aic.10025

Regulation of fatty acid biosynthesis in Escherichia coli.
journal, January 1993

Fast Knoevenagel Condensations Catalyzed by an Artificial Schiff-Base-Forming Enzyme
journal, May 2016

  • Garrabou, Xavier; Wicky, Basile I. M.; Hilvert, Donald
  • Journal of the American Chemical Society, Vol. 138, Issue 22
  • DOI: 10.1021/jacs.6b00816

Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids
journal, March 2012

  • Zhang, Fuzhong; Carothers, James M.; Keasling, Jay D.
  • Nature Biotechnology, Vol. 30, Issue 4
  • DOI: 10.1038/nbt.2149

OptZyme: Computational Enzyme Redesign Using Transition State Analogues
journal, October 2013

Optimal protein library design using recombination or point mutations based on sequence-based scoring functions
journal, July 2007

  • Pantazes, R. J.; Saraf, M. C.; Maranas, C. D.
  • Protein Engineering Design and Selection, Vol. 20, Issue 8
  • DOI: 10.1093/protein/gzm030

OptMAVEn – A New Framework for the de novo Design of Antibody Variable Region Models Targeting Specific Antigen Epitopes
journal, August 2014

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

VMD: Visual molecular dynamics
journal, February 1996

    Sort by:
    [ × clear filter / sort ]

    Works referencing / citing this record:

    Microbial synthesis of medium-chain chemicals from renewables
    journal, December 2017

    • Sarria, Stephen; Kruyer, Nicholas S.; Peralta-Yahya, Pamela
    • Nature Biotechnology, Vol. 35, Issue 12
    • DOI: 10.1038/nbt.4022

    Carboxylic Ester Hydrolases in Bacteria: Active Site, Structure, Function and Application
    journal, November 2019

    • Oh, Changsuk; Kim, T. Doohun; Kim, Kyeong Kyu
    • Crystals, Vol. 9, Issue 11
    • DOI: 10.3390/cryst9110597

    PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore
    journal, September 2018

    From directed evolution to computational enzyme engineering—A review
    journal, September 2019

    • Chowdhury, Ratul; Maranas, Costas D.
    • AIChE Journal, Vol. 66, Issue 3
    • DOI: 10.1002/aic.16847

    Advanced strategy for metabolite exploration in filamentous fungi
    journal, January 2020

    PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore
    journal, September 2018

    Fatty Acid Biosynthesis: Chain‐Length Regulation and Control
    journal, June 2019

    • Heil, Christina S.; Wehrheim, S. Sophia; Paithankar, Karthik S.
    • ChemBioChem, Vol. 20, Issue 18
    • DOI: 10.1002/cbic.201800809

    Structure-guided protein engineering increases enzymatic activities of the SGNH family esterases
    journal, June 2020

    Computational redesign of penicillin acylase for cephradine synthesis with high kinetic selectivity
    journal, January 2018

    • He, Jinwen; Huang, Xiaoqiang; Xue, Jing
    • Green Chemistry, Vol. 20, Issue 24
    • DOI: 10.1039/c8gc03420f

    Recent advances in high-throughput mass spectrometry that accelerates enzyme engineering for biofuel research
    journal, February 2020

      Sort by:
      [ × clear filter / sort ]

      Figures / Tables found in this record:

      Figure 1 (p. 16)figure
      Figure 2 (p. 17)figure
      Figure 3 (p. 19)figure
      Figure 4 (p. 20)figure
      Figure 5 (p. 21)figure
      Figure 6 (p. 22)figure
      Figure 7 (p. 23)figure
      Table 1 (p. 24)table
      Figure S1 (p. 26)figure
      Figure S2 (p. 27)figure
      Figure S3 (p. 28)figure
      Figure S4 (p. 29)figure
      Figure S5 (p. 30)figure
      Table S1: Part 1 (p. 31)table
      Table S1: Part 2 (p. 32)table
      Table S1: Part 3 (p. 33)table
      Table S1: Part 4 (p. 34)table
      Table S1: Part 5 (p. 35)table
      Table S1: Part 6 (p. 36)table
      Table S1: Part 7 (p. 37)table
      Table S1: Part 8 (p. 38)table
      Table S2: Part 1 (p. 39)table
      Table S2: Part 2 (p. 40)table
      Table S2: Part 3 (p. 41)table
      Table S2: Part 4 (p. 42)table
      Table S3 (p. 43)table
      Table S4: Part 1 (p. 44)table
      Table S4: Part 2 (p. 45)table
      Table S4: Part 3 (p. 46)table
      Table S4: Part 4 (p. 47)table
      Table S4: Part 5 (p. 48)table
      Table S5 (p. 50)table
      Table S6 (p. 51)table
        [ × clear filter / sort ]
        Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.

        Similar Records in DOE PAGES and OSTI.GOV collections: