Gavin Williams
Synthetic biology, Natural products, Protein engineering, Metabolic engineering, Drug development
Works (55)
Updated: April 3rd, 2024 18:47
2023 article
Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products
Paulsel, T. Q., & Williams, G. J. (2023, September 15). CHEMBIOCHEM, Vol. 9.
author keywords: bioorganic chemistry; biosynthesis; enzymes; polyketides; synthetic biology
TL;DR:
These synthetic strategies have successfully yielded natural product derivatives while providing critical insights into enzymatic promiscuity and mechanistic activity and their contributions to the field of chemical biology are summarized.
(via Semantic Scholar)
onlinelibrary.wiley.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, ORCID
Added: October 10, 2023
2022 journal article
Targeted enzyme modifications enable regioselective biosynthesis of fluorinated polyketides
CHEM CATALYSIS, 2(10), 2440–2443.
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries
Added: January 17, 2023
2021 journal article
Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase
NATURE COMMUNICATIONS, 12(1).
MeSH headings : Acyltransferases / chemistry; Acyltransferases / genetics; Acyltransferases / metabolism; Catalytic Domain; Malonyl Coenzyme A; Molecular Dynamics Simulation; Mutagenesis; Polyketide Synthases / chemistry; Polyketide Synthases / genetics; Polyketide Synthases / metabolism; Polyketides; Protein Engineering; Secondary Metabolism; Substrate Specificity
TL;DR:
Molecular dynamics simulations are used to pinpoint mutations that impact AT domain selectivity and exchange structural motifs to obtain chimeric PKS modules with expanded substrate specificity, leading to identification of two previously unexplored structural motifS.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: April 14, 2021
2021 journal article
Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of Semisynthetic Macrolide Antibiotics
ACS SYNTHETIC BIOLOGY, 10(10), 2520–2531.
author keywords: macrolide; polyketide; biosensor; transcription factor; synthetic biology
MeSH headings : Anti-Bacterial Agents / biosynthesis; Anti-Bacterial Agents / chemistry; Biosensing Techniques / methods; Macrolides / chemistry; Macrolides / metabolism; Methyltransferases / metabolism; Molecular Structure; Mutagenesis
TL;DR:
It is shown that the effector specificity of the biosensor protein, MphR, can be evolved to selectively recognize clarithromycin and therefore report on the production of this molecule in vivo.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: ORCID, Web Of Science, NC State University Libraries
Added: September 22, 2021
2021 review
Protein engineering for natural product biosynthesis and synthetic biology applications
[Review of ]. PROTEIN ENGINEERING DESIGN & SELECTION, 34.
author keywords: biosynthesis; natural products; peptides; polyketides; synthetic biology; terpenes
MeSH headings : Biocatalysis; Biological Products; Peptides / metabolism; Protein Engineering; Synthetic Biology
TL;DR:
This work details the most recent advances, focusing on polyketides, non-ribosomal peptides and isoprenoids, including their native biosynthetic logic to provide clarity for future applications of these technologies for natural product synthetic biology.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries
Added: September 27, 2021
2021 review
Transcription factor-based biosensors: a molecular-guided approach for natural product engineering
[Review of ]. CURRENT OPINION IN BIOTECHNOLOGY, 69, 172–181.
MeSH headings : Biological Products; Biosensing Techniques; Biosynthetic Pathways; High-Throughput Screening Assays; Metabolic Engineering; Transcription Factors / genetics
TL;DR:
The development and application of engineered allosteric transcription factor-based biosensors is described that enable optimization of precursor availability, product titers, and downstream product tailoring for advancing the natural product bioeconomy.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries
Added: July 26, 2021
2020 journal article
An artificial pathway for polyketide biosynthesis
Nature Catalysis, 3(7), 536–538.
TL;DR:
Some of the inefficiencies and limitations of these systems have been solved by designing an artificial pathway for carbon–carbon bond formation via iterative rounds of non-decarboxylative thio-Claisen reactions.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 3, 2020
2020 journal article
Cheminformatics Analysis and Modeling with MacrolactoneDB
Scientific Reports, 10(1).
MeSH headings : Biological Products / chemistry; Cheminformatics; Databases, Chemical; Machine Learning; Macrolides / chemistry; Models, Chemical; Quantitative Structure-Activity Relationship; Software
TL;DR:
This study develops MacrolactoneDB, which integrates nearly 14,000 existing macrolactones and their bioactivity information from different public databases, and new molecular descriptors to better characterize macrolide structures, and shows that merging descriptors yields the best predictive power with Random Forest models.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
15. Life on Land
(OpenAlex)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: September 7, 2020
2020 article
Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase
Kalkreuter, E., Bingham, K. S., Keeler, A. M., Lowell, A. N., Schmidt, J. J., Sherman, D. H., & Williams, G. J. (2020, April 25). (Vol. 4). Vol. 4.
Source: ORCID
Added: December 15, 2020
2020 journal article
SIME: synthetic insight-based macrolide enumerator to generate the V1B library of 1 billion macrolides
Journal of Cheminformatics, 12(1).
author keywords: Macrolides; PKS enumerator; In silico chemical library software; Polyketides
TL;DR:
A new cheminformatics enumeration technology—SIME, synthetic insight-based macrolide enumerator—a new and improved software technology that can enumerate fully assembled macrolides with synthetic feasibility by utilizing the constitutional and structural knowledge extracted from biosynthetic aspects of macrolided.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: April 27, 2020
2020 journal article
Synthetic biology enabling access to designer polyketides
Current Opinion in Chemical Biology, 58, 45–53.
author keywords: Polyketides; Synthetic biology; Metabolic engineering; Enzyme engineering; Natural products
MeSH headings : Genetic Engineering; Multigene Family; Polyketides / chemistry; Polyketides / metabolism; Synthetic Biology / methods
TL;DR:
Recent successes in gene cluster discovery, host strain engineering, precursor-directed biosynthesis, combinatorial biosynthesis), polyketide tailoring, and high-throughput synthetic biology are discussed, as well as challenges and outlooks for rapidly generating useful target polyketides.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Crossref, NC State University Libraries, Web Of Science
Added: December 22, 2020
2020 article
Synthetic biology, combinatorial biosynthesis, and chemo-enzymatic synthesis of isoprenoids (September, 10.1007/s10295-020-02306-3, 2020)
Malico, A. A., Calzini, M. A., Gayen, A. K., & Williams, G. J. (2020, December). JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY, Vol. 47, pp. 1181–1181.
TL;DR:
The article title was published incorrectly in the HTML version (online version only) of the online published article.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: November 30, 2020
2020 journal article
Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids
Journal of Industrial Microbiology & Biotechnology, 47(9-10), 675–702.
author keywords: Isoprenoids; Terpenes; Synthetic biology; Combinatorial biosynthesis; Hemiterpenes
MeSH headings : Biological Products; Hemiterpenes; Synthetic Biology; Terpenes / chemistry
TL;DR:
This review summarizes recent advances and strategies related to isoprenoid synthetic biology, combinatorial biosynthesis, and chemo-enzymatic synthesis, focusing on the past 5 years, as well as emerging applications of cell-free biosynthesis and high-throughput tools.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, Crossref, NC State University Libraries
Added: September 21, 2020
2019 journal article
An Artificial Pathway for Isoprenoid Biosynthesis Decoupled from Native Hemiterpene Metabolism
ACS Synthetic Biology, 8(2), 232–238.
author keywords: isoprenoids; terpenoids; hemiterpene; kinase; lycopene; prenyltransferase
MeSH headings : Biosynthetic Pathways; Dimethylallyltranstransferase / metabolism; Hemiterpenes / metabolism; Lycopene / metabolism; Metabolic Engineering; Terpenes / metabolism
TL;DR:
An artificial alcohol-dependent hemiterpene biosynthetic pathway was designed and coupled to several isoprenoid biosynthesis systems, affording lycopene and a prenylated tryptophan in robust yields.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: March 11, 2019
2019 journal article
Cover Feature: Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production (ChemBioChem 17/2019)
ChemBioChem, 8.
Source: ORCID
Added: December 15, 2020
2019 journal article
Development of a Genetically Encoded Biosensor for Detection of Polyketide Synthase Extender Units in Escherichia coli
ACS Synthetic Biology, 8(6), 1391–1400.
MeSH headings : Biosensing Techniques / methods; Escherichia coli / genetics; Escherichia coli Proteins / genetics; Escherichia coli Proteins / isolation & purification; Escherichia coli Proteins / metabolism; Malonyl Coenzyme A / analysis; Malonyl Coenzyme A / metabolism; Metabolic Networks and Pathways; Polyketide Synthases / metabolism; Polyketides / metabolism; Protein Engineering / methods; Recombinant Proteins / genetics; Recombinant Proteins / isolation & purification; Recombinant Proteins / metabolism; Synthetic Biology; Transcription Factors / genetics; Transcription Factors / isolation & purification; Transcription Factors / metabolism
TL;DR:
The previously unknown broad effector promiscuity of FapR provides a platform to develop new tools and approaches that can be leveraged to overcome limitations of pathways that construct diverse α-carboxyacyl-CoAs and those that are dependent on them, including biofuels, antibiotics, anticancer drugs, and other value-added products.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: July 15, 2019
2019 journal article
Engineering the Substrate Specificity of a Modular Polyketide Synthase for Installation of Consecutive Non-Natural Extender Units
Journal of the American Chemical Society, 141(5), 1961–1969.
MeSH headings : Molecular Structure; Polyketide Synthases / chemistry; Polyketide Synthases / metabolism; Protein Engineering; Substrate Specificity
TL;DR:
AT engineering provided the first full-length polyketide products incorporating two non-natural extender units and the identification of previously poorly characterized bottlenecks provides a platform for future advancements in the field.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: February 25, 2019
2019 journal article
Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production
ChemBioChem, 20(17), 2217–2221.
author keywords: hemiterpenes; kinases; phosphorylation; synthetic biology; terpenoids
MeSH headings : Alcohols; Diphosphates / metabolism; Hemiterpenes / chemical synthesis; Phosphates / metabolism; Protein Kinases / metabolism; Substrate Specificity; Synthetic Biology / methods; Terpenes / chemical synthesis; Thermoplasma / enzymology
TL;DR:
For the first time, the promiscuity of the second enzyme in the ADH pathway—isopentenyl phosphate kinase from Thermoplasma acidophilum—is probed, and the suitability of this enzyme to provide unnatural pyrophosphates is evaluated, to provide a critical first step in characterizing the rate‐limiting steps in the artificialADH pathway.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 12, 2019
2019 article
Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production
Lund, S., Courtney, T., & Williams, G. (2019, February 26). (Vol. 2). Vol. 2.
Source: ORCID
Added: October 25, 2021
2018 journal article
Cheminformatics-based enumeration and analysis of large libraries of macrolide scaffolds
Journal of Cheminformatics, 10(1).
TL;DR:
A cheminformatics approach and associated software that allows for designing and generating libraries of virtual macrocycle/macrolide scaffolds with user-defined constitutional and structural constraints and the chemical diversity and distribution of structural motifs in V1M library is introduced.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: December 3, 2018
2018 journal article
Development of Transcription Factor-Based Designer Macrolide Biosensors for Metabolic Engineering and Synthetic Biology
ACS Synthetic Biology, 7(1), 227–239.
MeSH headings : Actinobacteria / drug effects; Actinobacteria / growth & development; Binding Sites; Biosensing Techniques; Directed Molecular Evolution; Erythromycin / biosynthesis; Erythromycin / pharmacology; Ligands; Macrolides / metabolism; Metabolic Engineering; Molecular Dynamics Simulation; Mutagenesis; Protein Structure, Tertiary; Synthetic Biology / methods; Transcription Factors / chemistry; Transcription Factors / genetics; Transcription Factors / metabolism
TL;DR:
It is shown that the promiscuous macrolide sensing transcription factor MphR is a powerful platform for engineering variants with tailored properties that displayed improved sensitivity toward erythromycin, tailored the inducer specificity, and significantly improved sensitivity to macrolides that were very poor inducers of the wild-type MphC biosensor.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Crossref, ORCID, NC State University Libraries
Added: November 29, 2020
2018 journal article
Engineering enzymatic assembly lines for the production of new antimicrobials
Current Opinion in Microbiology, 45, 140–148.
MeSH headings : Anti-Infective Agents / chemical synthesis; Anti-Infective Agents / chemistry; Anti-Infective Agents / metabolism; Bacterial Proteins / chemistry; Bacterial Proteins / genetics; Bacterial Proteins / metabolism; Metabolic Engineering; Peptide Synthases / chemistry; Peptide Synthases / genetics; Peptide Synthases / metabolism; Polyketide Synthases / chemistry; Polyketide Synthases / genetics; Polyketide Synthases / metabolism; Synthetic Biology
TL;DR:
The field is likely nearing the ability to design and build new biosynthetic pathways de novo, with various recent approaches taken towards this goal, focusing on the installation of new substrates, the swapping of enzymatic domains and modules, and the impact of metabolic engineering and synthetic biology.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: January 21, 2019
2018 journal article
Extender Unit Promiscuity and Orthogonal Protein Interactions of an Aminomalonyl-ACP Utilizing Trans-Acyltransferase from Zwittermicin Biosynthesis
ACS Chemical Biology, 13(12), 3361–3373.
MeSH headings : Acyl Carrier Protein / chemistry; Acyl Carrier Protein / genetics; Acyl Carrier Protein / metabolism; Acyltransferases / chemistry; Acyltransferases / genetics; Acyltransferases / metabolism; Bacillus thuringiensis / enzymology; Bacillus thuringiensis / genetics; Bacterial Proteins / chemistry; Bacterial Proteins / genetics; Bacterial Proteins / metabolism; Base Sequence; Catalytic Domain; Coenzyme A Ligases / metabolism; Escherichia coli / genetics; Kinetics; Molecular Docking Simulation; Molecular Dynamics Simulation; Polyketide Synthases / chemistry; Polyketide Synthases / genetics; Polyketide Synthases / metabolism; Protein Binding; Protein Engineering / methods; Rhizobium / enzymology; Substrate Specificity; Transferases (Other Substituted Phosphate Groups) / metabolism
TL;DR:
A method to access a panel of non-natural and non-native ACP-linked extender units was developed and used to probe the promiscuity of ZmaF, revealing one of the most promiscuous ATs characterized to date.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: January 14, 2019
2017 journal article
Direct analysis of terpenes from biological buffer systems using SESI and IR-MALDESI
Analytical and Bioanalytical Chemistry, 410(3), 953–962.
author keywords: Terpenes; IR-MALDESI; SESI; Direct analysis; Biological buffers; Q Exactive Plus
MeSH headings : Alkenes / analysis; Buffers; Infrared Rays; Ions / analysis; Monocyclic Sesquiterpenes; Sesquiterpenes / analysis; Spectrometry, Mass, Electrospray Ionization / methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods; Terpenes / analysis
TL;DR:
By coupling the two techniques and doping the electrospray solvent with silver ions, olefinic terpenes of different classes and varying degrees of volatility were directly analyzed from a biological buffer system with no sample workup steps.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2017 journal article
Inversion of Extender Unit Selectivity in the Erythromycin Polyketide Synthase by Acyltransferase Domain Engineering
ACS Chemical Biology, 12(1), 114–123.
MeSH headings : Acyltransferases / chemistry; Acyltransferases / genetics; Acyltransferases / metabolism; Erythromycin / chemistry; Erythromycin / metabolism; Macrolides / chemistry; Macrolides / metabolism; Mutagenesis, Site-Directed / methods; Point Mutation; Polyketide Synthases / chemistry; Polyketide Synthases / genetics; Polyketide Synthases / metabolism; Polyketides / chemistry; Polyketides / metabolism; Protein Domains; Saccharopolyspora / enzymology; Saccharopolyspora / genetics; Saccharopolyspora / metabolism; Substrate Specificity
TL;DR:
The strategy and mutations described herein form a platform for combinatorial biosynthesis of site-selectively modified polyketide analogues that are modified with non-natural and non-native chemical functionality.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: ORCID, Crossref, NC State University Libraries
Added: December 15, 2020
2017 journal article
Polyketide Bioderivatization Using the Promiscuous Acyltransferase KirCII
ACS Synthetic Biology, 6(3), 421–427.
author keywords: antibiotic; kirromycin; polyketide synthase; trans-acyltransferase; engineering click chemistry
MeSH headings : Acyltransferases / metabolism; Anti-Bacterial Agents / metabolism; Bacteria / metabolism; Bacterial Proteins / metabolism; Polyketide Synthases / metabolism; Polyketides / metabolism; Pyridones / metabolism
TL;DR:
This work exploits the promiscuity of KirCII to generate new kirromycins with allyl- and propargyl-side chains in vivo, and the latter were utilized as educts for further modification by "click" chemistry.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2015 journal article
Harnessing natural product assembly lines: structure, promiscuity, and engineering
Journal of Industrial Microbiology & Biotechnology, 43(2-3), 371–387.
author keywords: Combinatorial biosynthesis; Synthetic biology; Enzyme engineering; Polyketide synthases; Non-ribosomal peptide synthases
MeSH headings : Biological Products / chemistry; Biological Products / metabolism; Biosynthetic Pathways / genetics; Metabolic Engineering; Peptides / metabolism; Polyketides / metabolism
TL;DR:
This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2015 journal article
Harnessing the promiscuity of natural product biosynthesis: A platform for engineering pathways with new specificities
Planta Medica, 81(11).
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2014 journal article
Evaluating nonpolar surface area and liquid chromatography/mass spectrometry response: an application for site occupancy measurements for enzyme intermediates in polyketide biosynthesis
Rapid Communications in Mass Spectrometry, 28(23), 2511–2522.
MeSH headings : Acyltransferases / metabolism; Chromatography, Liquid / methods; Filtration; Hydrophobic and Hydrophilic Interactions; Mass Spectrometry / methods; Oligopeptides / chemistry; Oligopeptides / metabolism; Peptide Fragments / chemistry; Peptide Fragments / metabolism; Polyketides / chemistry; Polyketides / metabolism
TL;DR:
The MS signal as a function of nonpolar surface area (NPSA) is explored in order to better understand this bias in electrospray response and to determine relative LC/MS response for peptides.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2014 journal article
Intracellular Light-Activation of Riboswitch Activity
ChemBioChem, 15(9), 1346–1351.
author keywords: chemical biology; photocontrol; riboswitches; RNA; synthetic biology
MeSH headings : Cell Membrane Permeability; Gene Expression Regulation / drug effects; Gene Expression Regulation / radiation effects; Intracellular Space / drug effects; Intracellular Space / genetics; Intracellular Space / radiation effects; Ligands; Molecular Structure; Riboswitch / drug effects; Riboswitch / genetics; Riboswitch / radiation effects; Structure-Activity Relationship; Theophylline / chemistry; Theophylline / pharmacology; Ultraviolet Rays
TL;DR:
By combining a riboswitch with a cell‐permeable photocaged small‐molecule ligand, an optochemical gene control element was constructed that enabled spatial and temporal control of gene expression in bacterial cells.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2014 journal article
Mapping a Ketosynthase:Acyl Carrier Protein Binding Interface via Unnatural Amino Acid-Mediated Photo-Cross-Linking
Biochemistry, 53(48), 7494–7502.
MeSH headings : Acetyltransferases / chemistry; Acetyltransferases / genetics; Acetyltransferases / metabolism; Acyl Carrier Protein / chemistry; Acyl Carrier Protein / genetics; Acyl Carrier Protein / metabolism; Bacterial Proteins / chemistry; Bacterial Proteins / genetics; Bacterial Proteins / metabolism; Conserved Sequence; Cross-Linking Reagents; Escherichia coli / genetics; Escherichia coli / metabolism; Escherichia coli Proteins / chemistry; Escherichia coli Proteins / genetics; Escherichia coli Proteins / metabolism; Fatty Acid Synthase, Type II / chemistry; Fatty Acid Synthase, Type II / genetics; Fatty Acid Synthase, Type II / metabolism; Models, Molecular; Mutagenesis, Site-Directed; Open Reading Frames; Photochemical Processes; Protein Interaction Domains and Motifs; Saccharopolyspora / genetics; Saccharopolyspora / metabolism; Streptomyces coelicolor / genetics; Streptomyces coelicolor / metabolism
TL;DR:
Unnatural amino acid mutagenesis is used to site specifically install photo-cross-linking functionality into acyl carrier proteins from diverse systems and the ketosynthase FabF from the Escherichia coli type II fatty acid synthase to demonstrate that unnatural amino acid based photo-Cross-l linking is a powerful tool for probing and interrogating protein interactions in complex biosynthetic systems.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2014 journal article
Reprogramming Acyl Carrier Protein Interactions of an Acyl-CoA Promiscuous trans-Acyltransferase
Chemistry & Biology, 21(5), 636–646.
MeSH headings : Acyl Carrier Protein / metabolism; Acyl Coenzyme A / metabolism; Acyltransferases / metabolism; Molecular Structure; Pyridones / metabolism
TL;DR:
An assay to probe ACP interactions based on leveraging the extender unit promiscuity of KirCII is developed and allows us to identify residues on the ACP surface that contribute to specific recognition by KirC II.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2014 conference paper
Synthetic Biology Approaches For Combinatorial Biosynthesis Of Polyketide Natural Products.
Abstracts of Papers for the American Chemical Society. Presented at the 247th National Spring Meeting of the American Chemical Society, Dallas, Texas, USA.
Event: 247th National Spring Meeting of the American Chemical Society at Dallas, Texas, USA on March 16, 2014
Source: NC State University Libraries
Added: December 30, 2020
2013 journal article
Engineering polyketide synthases and nonribosomal peptide synthetases
Current Opinion in Structural Biology, 23(4), 603–612.
MeSH headings : Antineoplastic Agents / chemical synthesis; Antineoplastic Agents / metabolism; Gene Expression; Mutagenesis, Site-Directed / methods; Peptide Biosynthesis, Nucleic Acid-Independent; Peptide Synthases / metabolism; Polyketide Synthases / metabolism; Polyketides / chemical synthesis; Protein Engineering / methods
TL;DR:
This review highlights strategies based on site-directed mutagenesis of substrate binding pockets, semi-rational mutagenization, and whole-gene random mutagenisation to engineer the substrate specificity, activity, and protein interactions of polyketide and nonribosomal peptide biosynthetic machinery.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2013 journal article
Promiscuity of a modular polyketide synthase towards natural and non-natural extender units
Organic & Biomolecular Chemistry, 11(27), 4449.
MeSH headings : Acyl Coenzyme A / chemistry; Acyl Coenzyme A / metabolism; Bacterial Proteins / chemistry; Bacterial Proteins / metabolism; Coenzyme A Ligases / chemistry; Coenzyme A Ligases / metabolism; Polyketide Synthases / chemistry; Polyketide Synthases / metabolism; Protein Structure, Tertiary; Rhizobium / chemistry; Rhizobium / enzymology; Rhizobium / metabolism; Substrate Specificity
TL;DR:
A panel of chemo-enzymatically synthesized acyl-CoA's was used to probe the promiscuity of a polyketide synthase, revealing that the KS is remarkably tolerant to a diverse array of extender units, while the AT likely discriminates betweenextender units that are native to the producing organism.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
10. Reduced Inequalities
(OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2013 chapter
Reprogramming the Biosynthesis of Natural Products by Directed Evolution
In A. Kantardjieff, P. Asuri, J. L. Coffman, & K. Jayapal (Eds.), Developments in Biotechnology and Bioprocessing (pp. 147–163).
Ed(s): A. Kantardjieff, P. Asuri, J. Coffman & K. Jayapal
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2012 chapter
Engineering Glycosyltransferases
In S. Lutz & U. T. Bornscheuer (Eds.), The Protein Engineering Handbook (Vol. 3, pp. 303–326). Weinheim: Wiley-HCH.
Ed(s): S. Lutz & U. Bornscheuer
Source: NC State University Libraries
Added: December 30, 2020
2012 journal article
Poly Specific trans-Acyltransferase Machinery Revealed via Engineered Acyl-CoA Synthetases
ACS Chemical Biology, 8(1), 200–208.
MeSH headings : Acyltransferases / chemistry; Acyltransferases / genetics; Bacterial Proteins / chemistry; Bacterial Proteins / genetics; Chromatography, Liquid; Coenzyme A Ligases / chemistry; Coenzyme A Ligases / genetics; Crystallography, X-Ray; Genetic Variation; Models, Molecular; Substrate Specificity
TL;DR:
Results reveal that polyketide biosynthetic machinery might be more tolerant to non-natural substrates than previously established, and that mutant synthetases are valuable tools for probing the specificity of biosynthetics machinery.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2012 conference paper
Reprogramming the biosynthesis of natural products by directed evolution.
Abstracts of Papers of the American Chemical Society. Presented at the 243rd National Spring Meeting of the American Chemical Society, San Diego, CA, USA.
Event: 243rd National Spring Meeting of the American Chemical Society at San Diego, CA, USA on March 25, 2012
Source: NC State University Libraries
Added: December 30, 2020
2011 journal article
A High-Throughput Screen for Directed Evolution of the Natural Product Sulfotransferase LipB
Journal of Biomolecular Screening, 16(8), 845–851.
author keywords: chemistry; medicinal; organic; synthetic; and combinatorial; enzyme assays or enzyme kinetics; anti-infective drugs; natural products screening
MeSH headings : Acyltransferases / chemistry; Acyltransferases / genetics; Acyltransferases / metabolism; Aminoglycosides / metabolism; Biocatalysis; Biological Products / chemistry; Biological Products / metabolism; Biotransformation; Cloning, Molecular; Colorimetry; Escherichia coli / chemistry; Escherichia coli / enzymology; Escherichia coli / genetics; Escherichia coli Proteins / chemistry; Escherichia coli Proteins / genetics; Escherichia coli Proteins / metabolism; Gene Library; High-Throughput Screening Assays; Nitrobenzenes / analysis; Nitrobenzenes / metabolism; Plasmids; Recombinant Proteins / chemistry; Recombinant Proteins / genetics; Recombinant Proteins / metabolism; Small Molecule Libraries / analysis; Small Molecule Libraries / chemistry; Substrate Specificity
TL;DR:
A colorimetric, high-throughput assay suitable for optimizing the activity of the recently discovered sulfotransferase LipB, by directed evolution is described and plans to use the screen to identify LipB variants with altered acceptor specificity and promiscuity for use in sulfation of natural products and other small-molecule therapeutics.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, NC State University Libraries, Crossref
Added: August 6, 2018
2011 journal article
A high-throughput screen for directed evolution of aminocoumarin amide synthetases
Analytical Biochemistry, 419(1), 61–66.
author keywords: Directed evolution; Aminocoumarin; High-throughput screening; Natural products
MeSH headings : Acylation; Amide Synthases / metabolism; Aminocoumarins / chemistry; Aminocoumarins / metabolism; Chromatography, High Pressure Liquid; Cloning, Molecular; Directed Molecular Evolution / methods; Enzyme Activation; Escherichia coli / genetics; Escherichia coli / metabolism; Fluorescence; Fluorometry / methods; High-Throughput Screening Assays / methods; Molecular Structure; Novobiocin / analogs & derivatives; Novobiocin / chemistry; Novobiocin / metabolism; Plasmids / genetics; Plasmids / metabolism; Reproducibility of Results; Substrate Specificity
TL;DR:
A fluorimetric high-throughput screen is designed and validated, which can be used to report the activity of mutant amide synthetases toward a broad range of coumarin and acyl donor substrates, and is anticipated to accelerate the creation of amid synthetase mutants with new specificities by directed evolution.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2011 journal article
A photocrosslinking assay for reporting protein interactions in polyketide and fatty acid synthases
Molecular BioSystems, 7(11), 3152.
MeSH headings : Acyl Carrier Protein / chemistry; Acyl Carrier Protein / metabolism; Codon, Terminator; Cross-Linking Reagents / chemistry; Cross-Linking Reagents / metabolism; Fatty Acid Synthases / chemistry; Fatty Acid Synthases / metabolism; Kinetics; Mutagenesis, Site-Directed; Polyketide Synthases / chemistry; Polyketide Synthases / metabolism; Polyketides / metabolism; Protein Conformation
TL;DR:
This work reports a facile strategy for rapidly reporting such ACP-KS interactions based on the incorporation of an amino acid with photocrosslinking functionality that can be applied to any polyketide or fatty acid synthase regardless of substrate specificity.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2011 journal article
Inside Cover: Mutant Malonyl-CoA Synthetases with Altered Specificity for Polyketide Synthase Extender Unit Generation (ChemBioChem 15/2011)
ChemBioChem, 12(15), 2230–2230.
Sources: ORCID, Crossref, NC State University Libraries
Added: December 15, 2020
2011 journal article
Mutant Malonyl-CoA Synthetases with Altered Specificity for Polyketide Synthase Extender Unit Generation
ChemBioChem, 12(15), 2289–2293.
author keywords: directed evolution; enzymes; polyketides; protein engineering; specificity
MeSH headings : Bacterial Proteins / genetics; Bacterial Proteins / metabolism; Cloning, Molecular; Coenzyme A Ligases / genetics; Coenzyme A Ligases / metabolism; Mutagenesis; Mutant Proteins / genetics; Mutant Proteins / metabolism; Polyketide Synthases / metabolism; Rhizobium / enzymology; Rhizobium / genetics; Substrate Specificity
TL;DR:
This work has used structure-guided saturation mutagenesis followed by colorimetric screening to identify mutant malonyl-CoA synthetases with altered substrate specificity with a 240-fold shift in specificity.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Sources: Web Of Science, ORCID, NC State University Libraries, Crossref
Added: August 6, 2018
2011 journal article
Recombinant E. coli Prototype Strains for in Vivo Glycorandomization
ACS Chemical Biology, 6(1), 95–100.
MeSH headings : Biological Products / chemistry; Biological Products / metabolism; Carbohydrate Metabolism; Carbohydrates / chemistry; Catalysis; Escherichia coli / classification; Escherichia coli / enzymology; Escherichia coli / genetics; Escherichia coli / metabolism; Glycosylation; Glycosyltransferases / chemistry; Glycosyltransferases / metabolism; Nucleotidyltransferases / chemistry; Nucleotidyltransferases / metabolism; Protein Engineering; Recombinant Proteins; Substrate Specificity
TL;DR:
This work reports the construction of several recombinant E. coli prototype strains that allow the facile production of a range of small molecule glycosides and offers vast combinatorial potential by simple fermentation.
(via Semantic Scholar)
Sources: ORCID, Crossref, NC State University Libraries
Added: December 15, 2020
2009 chapter
Natural Product Glycosyltransferases: Properties and Applications
In Advances in Enzymology - and Related Areas of Molecular Biology (pp. 55–119).
MeSH headings : Aminocoumarins / metabolism; Aminoglycosides / metabolism; Anthracyclines / metabolism; Directed Molecular Evolution; Drug Design; Enediynes / metabolism; Enterobactin / metabolism; Erythromycin / metabolism; Glycosyltransferases / chemistry; Glycosyltransferases / metabolism; Ivermectin / analogs & derivatives; Ivermectin / metabolism; Lactams / metabolism; Macrolides / metabolism; Models, Molecular; Oleandomycin / metabolism; Protein Engineering; Teicoplanin / metabolism; Vancomycin / analogs & derivatives; Vancomycin / metabolism
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2008 journal article
A high-throughput fluorescence-based glycosyltransferase screen and its application in directed evolution
Nature Protocols, 3(3), 357–362.
MeSH headings : Bacterial Proteins / genetics; Biomedical Engineering / methods; Directed Molecular Evolution / methods; Escherichia coli / genetics; Fluorescence; Gene Library; Glucosyltransferases / genetics; Glycosylation; Glycosyltransferases / analysis; Glycosyltransferases / metabolism; Mutagenesis / genetics; Mutation / genetics; Streptomyces antibioticus / enzymology
TL;DR:
This protocol details the application of a high-throughput fluorescence-based screen, in conjunction with error-prone PCR/saturation mutagenesis, for altering the proficiency and/or promiscuity of a secondary metabolite glycosyltransferase (GT) via directed evolution.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2008 journal article
Optimizing Glycosyltransferase Specificity via “Hot Spot” Saturation Mutagenesis Presents a Catalyst for Novobiocin Glycorandomization
Chemistry & Biology, 15(4), 393–401.
MeSH headings : Amino Acid Substitution; Amino Acids; Binding Sites; Catalysis; Directed Molecular Evolution; Fluorescence; Glycosylation; Glycosyltransferases / chemistry; Glycosyltransferases / genetics; Glycosyltransferases / metabolism; Kinetics; Mutagenesis, Site-Directed / methods; Novobiocin / metabolism; Oleandomycin / metabolism; Substrate Specificity
TL;DR:
A comprehensive two-phase "hot spot" saturation mutagenesis strategy for the rapid evolution of glycosyltransferase (GT) specificity for nonnatural acceptors is described, which rapidly led to improvements in the desired catalytic activity of several hundred-fold.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2008 journal article
Probing the Aglycon Promiscuity of an Engineered Glycosyltransferase
Angewandte Chemie International Edition, 47(46), 8889–8892.
author keywords: carbohydrates; enzymes; glycosides; glycosylation; natural products
MeSH headings : Carbohydrate Metabolism; Carbohydrates / chemistry; Catalysis; Glycosyltransferases / metabolism; Molecular Structure; Protein Engineering; Streptomyces antibioticus / enzymology
TL;DR:
This study highlights the ability of OleD variants to glucosylate a total of 71 diverse acceptors, catalyze iterative glycosylation with numerous substrates, and establishes OleD as the first multifunctional GT capable of generating O-, S- and N-glycosides.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2008 journal article
The impact of enzyme engineering upon natural product glycodiversification
Current Opinion in Chemical Biology, 12(5), 556–564.
MeSH headings : Biological Products / chemical synthesis; Biological Products / chemistry; Biological Products / metabolism; Directed Molecular Evolution; Glycosylation; Glycosyltransferases / chemistry; Glycosyltransferases / metabolism; Humans; Protein Engineering / methods; Substrate Specificity
TL;DR:
This review highlights recent progress in the engineering/evolution of enzymes relevant to natural product glycodiversification with a particular focus upon GTs.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2007 journal article
Stereochemically Complementary Biocatalysts Created by Directed Evolution
Synfacts, 2007(2), 0208–0208.
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2006 journal article
Creation of a Pair of Stereochemically Complementary Biocatalysts
Journal of the American Chemical Society, 128(50), 16238–16247.
MeSH headings : Aldehydes / chemistry; Biomimetic Materials / chemistry; Biomimetic Materials / metabolism; Catalysis; Evolution, Molecular; Genetic Variation / genetics; Kinetics; Lyases / chemistry; Lyases / genetics; Lyases / metabolism; Models, Molecular; Molecular Structure; Mutation / genetics; N-Acetylneuraminic Acid / chemistry; N-Acetylneuraminic Acid / metabolism; Stereoisomerism
TL;DR:
Direct evolution was used to create a pair of stereochemically complementary variant NALs for the synthesis of sialic acid mimetics, and since residues identified as critical for stereoselectivity are conserved among members of the NAL superfamily, the approach might be extended to the evolution of other useful biocatalysts for the stereoselectedive synthesis of biologically active molecules.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2005 journal article
Structure-guided saturation mutagenesis of N-acetylneuraminic acid lyase for the synthesis of sialic acid mimetics
Protein Engineering, Design and Selection, 18(5), 239–246.
author keywords: N-acetylneuraminic acid lyase; sialic acid mimetics; structure-guided saturation mutagenesis; synthesis
MeSH headings : Amides / metabolism; Amino Acid Substitution; Biomimetics; Escherichia coli / enzymology; Molecular Structure; Mutagenesis; N-Acetylneuraminic Acid / metabolism; Oxo-Acid-Lyases / chemistry; Oxo-Acid-Lyases / genetics; Protein Engineering; Structure-Activity Relationship; Substrate Specificity
TL;DR:
Engineering efforts provide a scaffold for the further tailoring of NAL for the synthesis of sialic acid mimetics, including 6-dipropylcarboxamides, through structure-guided saturation mutagenesis.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
2003 journal article
Directed evolution: Creating new enzymes
The Biochemist, 25(4), 13–15.
Sources: NC State University Libraries, NC State University Libraries
Added: January 9, 2021
2003 journal article
Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution
Proceedings of the National Academy of Sciences, 100(6), 3143–3148.
MeSH headings : Aldehyde-Lyases / chemistry; Aldehyde-Lyases / genetics; Aldehyde-Lyases / metabolism; Catalytic Domain; Directed Molecular Evolution; Escherichia coli / genetics; Fructosediphosphates / chemistry; Fructosediphosphates / metabolism; Hexosediphosphates / chemistry; Hexosediphosphates / metabolism; Kinetics; Models, Molecular; Mutation; Nuclear Magnetic Resonance, Biomolecular; Recombinant Proteins / chemistry; Recombinant Proteins / genetics; Recombinant Proteins / metabolism; Stereoisomerism; Substrate Specificity
TL;DR:
It is shown that directed evolution can be used to alter the stereochemical course of the reaction catalyzed by tagatose-1,6-bisphosphate aldolase, resulting in a 100-fold change in stereospecificity.
(via Semantic Scholar)
Sources: Crossref, NC State University Libraries
Added: December 22, 2020
Employment
Updated: January 16th, 2021 10:20
2020 - present
North Carolina State University Raleigh, North Carolina, US
Professor
Chemistry
2015 - 2020
North Carolina State University Raleigh, North Carolina, US
Associate Professor
Chemistry
2009 - 2015
North Carolina State University Raleigh, North Carolina, US
Assistant Professor
Chemistry
Education
Updated: June 25th, 2014 11:36
University of Leeds Leeds, Leeds, GB
PhD
Molecular Biology and Biochemistry
Funding History
Funding history based on the linked ORCID record. Updated: January 16th, 2021 10:24
grant
March 17, 2020
Sery-CRISPR: A Novel Tool for Genome Editing
North Carolina Biotechnology Center
grant
September 1, 2019 - August 31, 2022
MRI: Acquisition of a flow cytometer to promote microbe-focused research, training, and teaching at NC State University
Directorate for Biological Sciences
grant
May 5, 2018 - February 28, 2022
Designer biosensors for directed evolution of macrolide biosynthetic enzymes
National Institute of General Medical Sciences
grant
June 6, 2017
Massively Paralleled Engineering of Antibiotic-producing Microbes Via Made-to-measure Genetically-encoded Biosensors
North Carolina Biotechnology Center
grant
June 15, 2013 - May 31, 2018
Synthetic Biology Approach to Regioselectively Modified Polyketides
National Institute of General Medical Sciences
grant
April 1, 2012 - March 31, 2017
CAREER: Reprogramming Polyketide Biosynthesis
National Science Foundation
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