John Honek

Professor, Chemistry

Research interests: bionanotechnology, mechanistic enzymology; recombinant DNA and biophysical methods; medicinal chemistry and molecular modeling

Biography

Professor John Honek developed novel amino acid analogs used to investigate protein structure/function and control metalloenzyme activity and uniquely applies biological chemistry to areas of nanotechnology such as bioencapsulation and biomaterial interfaces.

The Honek Lab, operating within the University of Waterloo Chemistry department, works at the interface of chemistry and biochemistry. Group members apply chemical and biochemical principles and techniques to the problems of protein structure/function as well as to elucidate the chemical mechanisms of several key enzymes, some of which have medical importance.

Honek received his BSc (Honours Chemistry) from McGill University in 1977, and obtained his PhD (Chemistry) in 1984 also from McGill University under the direction of the late Professor Bernard Belleau, one of the discoverers of the anti-AIDS drug 3TC. Honek took up FCAC (Québec) and Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowships to continue his studies (1984, 1985) under the direction of Professor Christopher Walsh at Massachusetts Institute of Technology (MIT), U.S.A., where he worked on the biochemistry of biogenic methane production. Honek joined the University of Waterloo Chemistry department in 1986 and held the role of Chemistry Department Chair from 2007 to 2014.

Professor Honek is on the editorial board of several journals including:

Molecules; Letters in Drug Design and Discovery, Current Medicinal Chemistry, Frontiers in Chemistry (Chemical Biology), Future Medicinal Chemistry, Biochemistry and Cell Biology (NRC)
Canadian Representative to the Organic & Biomolecular Chemistry Division, Synthesis Subcommittee, IUPAC

Cross-appointed to UW Pharmacy

Education

Postdoctoral Fellow: Massachusetts Institute of Technology
PhD, Chemistry, McGill University, 1984
BSc, Chemistry, McGill University, 1977

John Honek

Awards and Honours

Year	Awards and Honours
2014	Canadian Society for Chemistry (CSC) Bernard Belleau Award, sponsored by Vertex Pharmaceuticals (Canada) Inc.

Research

Areas of focus

Professor Honek’s interest is to understand the fundamental interactions of small molecules (such as substrates and drugs) with enzymes as well as the mechanisms by which enzymes catalyze reactions. Research in this area includes mechanistic enzymology, recombinant DNA and biophysical methods as well as organic synthesis, medicinal chemistry and molecular modeling. An additional focus is in the area of bionanotechnology and the application of biological chemistry to the synthesis of new nanomaterials and nanostructures.

Biological chemistry of the carbon-sulfur bond

Knowledge of an enzyme’s catalytic mechanism can be of fundamental importance as well as a critical factor in the design and synthesis of inhibitors having therapeutic potential. The group is currently focused on the biological chemistry of the carbon-sulfur bond as it relates to the amino acid methionine and its biochemical function in proteins as well as the study of the enzyme glyoxalase I, a detoxification metalloenzyme that utilizes a sulfur-containing cofactor, glutathione.

Bionanotechnology

Two areas are of current interest. The first is the investigation of extremely large multisubunit proteins which contain internal cavities. These nanosized proteins may be useful as novel drug carriers and as molecular foundations for nanodevices. The second area is the study of the molecular level interactions between biomolecules and nanomaterials. We have utilized phage display methods and unnatural amino acid incorporation techniques to identify peptide sequences that have strong affinity to single-walled carbon nanotubes.

Research interests

Biochemistry
Bioorganic/biological chemistry
Medicinal chemistry
Bionanotechnology

Publications

Recent publications include:

T. Urquhart, B. Howie, L. Zhang, K. T. Leung, and J. F. Honek, 2020, Bioconjugation of Bacteriophage Pf1 and Extension to Pf1-Based Bionanomaterials. Current Nanoscience, in press.
U. Suttisansanee and J. F. Honek, 2019, Preliminary Characterization of a Ni2+-Activated and Mycothiol-dependent Glyoxalase I Enzyme from Streptomyces coelicolor. Inorganics (Special Issue: Bioinorganic Chemistry of Nickel), 7(8), 99. doi.org/10.3390/inorganics7080099
Y. Hu, J. F. Honek, B. C. Wilson and Q-B. Lu, 2019, Synthesis and Photo-Cytotoxicity of Upconversion Nanoparticles: Potential Applications for Near-Infrared Photodynamic and Photothermal Therapy. Journal of Biophotonics, 12(11), e201900111. doi.org/10.1002/jbio.201900129
J. F. Honek, 2019, Commentary on “Current Challenges in the Development of Vaccines
and Drugs Against Emerging Vector-borne Diseases” by Professor Kwang-sun Kim, Pusan National University, Republic of Korea. Current Medicinal Chemistry, 26, 3201-3204.
M. Lu, Q-B. Lu and J. F. Honek, 2017, Squarate-Based Carbocyclic Nucleosides: Syntheses, Computational Analyses and Anticancer/Antiviral Evaluation. Bioorganic and Medicinal Chemistry Letters, 27, 282-287.
U. Suttisansanee and J. F. Honek, 2017, Hydroxamate Inhibitor Profiling of Both Zn2+- and Ni2+-Activated Glyoxalase I Metalloenzymes Having Diverse Quaternary Structures. Letters in Drug Design and Discovery, 14, 843-852.
J. F. Honek, 2017, Nickel Glyoxalase I. Chapter 10 in The Biological Chemistry of Nickel. Kozlowski, H., Zamble, D., and Rowinska-Zyrek, M. Eds., Royal Society of Chemistry.
T. Urquhart, E. Daub and J. F. Honek, 2016, Bioorthogonal Modification of the Major Sheath Protein of Bacteriophage M13: Extending the Versatility of Bionanomaterial Scaffolds. Bioconjugate Chemistry (ACS), 27, 2276-2280.
M. D. Vaughan, Z. Su, E. Daub, and J. F. Honek, 2016, Intriguing Cellular Processing of a Fluorinated Amino Acid During Protein Biosynthesis in Escherichia coli. Organic and Biomolecular Chemistry, 14, 8942-8946.
J. F. Honek, 2015, Glyoxalase Biochemistry. Biomolecular Concepts, 6, 401-414.
C. L. Myers, E. G. Kuiper, P. C. Grant, J. Hernandez, G. L. Conn, and J. F. Honek, 2015, Functional Roles in S-Adenosyl-L-Methionine Binding and Catalysis for Active Site Residues of the Thiostrepton Resistance Methyltransferase. FEBS Letters, 589, 3263-3270.
J. F. Honek, 2015, Biological Chemistry of the Carbon-Sulfur Bond. Canadian Journal of Chemistry, 93, 1051-1060.
U. Suttisansanee, Y. Ran, K. Y. Mullings, N. Sukdeo, and J. F. Honek, 2015, Modulating Glyoxalase I Metal Selectivity by Deletional Mutagenesis: Underlying Structural Factors Contributing to Nickel Activation Profiles. Metallomics, 7, 605-612.
R. Bythell-Douglas, U. Suttisansanee, G. R. Flematti, M. Challenor, M. Lee, S. Panjikar, J. F. Honek and C. S. Bond, 2015, The Crystal Structure of a Homodimeric Pseudomonas Glyoxalase I Enzyme Reveals Asymmetric Metallation Commensurate with Half-of-Sites Activity. Chemistry - A European Journal, 21, 541-544.
C. L. Myers, J. Harris, J. C. K. Yeung, and J. F. Honek, 2014, Molecular Interactions Between Thiostrepton and the TipAS Protein from Streptomyces lividans. ChemBioChem, 15, 681-687.
A. Ward, A. Petrie, J. F. Honek, and Xiaowu Tang, 2014, Analyte-Dependent Sensing Mechanisms: The Fabrication and Characterization of a 32-Channel Array of SWCNT-TF Chemiresistive Sensors. IEEE Nanotechnology Magazine, 8(2), 29-37.
J. F. Honek, 2014, Bacterial Glyoxalase I Enzymes: Structural and Biochemical Investigations. Biochemical Society Transactions, 42, 479-484.
A. A. Petrie, A. M. van der Ven, and J. F. Honek, 2013, Nanomaterial-based Biosensors in Biosensors and Their Applications in Healthcare: Hot Topics, eBook, Future Science Ltd., U.K.
J. F. Honek, 2013, Aeruginolysin in Handbook of Proteolytic Enzymes 3rd Edition. Rawlings, N. D. and Salvesen, G. Eds., Elsevier Limited, 867-872.
M. Palmer, A. Chan, T. Dieckmann and J. Honek, (2012) Biochemical Pharmacology, Wiley-VCH.
K. Y. Mullings, N. Sukdeo, U. Suttisansanee, Y. Ran, and J. F. Honek, 2012, Ni2+-Activated Glyoxalase I from Escherichia coli: Substrate Specificity, Kinetic Isotope Effects and Evolution Within the βαβββ Superfamily. Journal of Inorganic Biochemistry, 108, 133-140.
U. Suttisansanee, K. Lau, S. Lagishetty, K. N. Rao, S. Swaminathan, J. M. Sauder, S. K. Burley and J. F. Honek, 2011, Structural Variation in Bacterial Glyoxalase I Enzymes: Investigation of the Metalloenzyme Glyoxalase I from Clostridium acetobutylicum. Journal of Biological Chemistry, 286, 38367-38374.
D. Pradhan, Z. Su, S. Sindhwani, J. Honek and K. T. Leung, 2011, Electrochemical Growth of ZnO Nanobelt-Like Structures at 0 oC: Synthesis, Characterization, and in-situ Glucose Oxidase Embedment. Journal of Physical Chemistry C, 115, 18149-18156.
I. A. Moya, G. D. Westrop, G. H. Coombs and J. F. Honek, 2011, Mechanistic Studies on the Enzymatic Processing of Fluorinated Methionine Analogs by Trichomonas vaginalis Methionine γ-Lyase. Biochemical Journal, 438, 513-521.
Z. Su, S. Zhu, A. Donkor, C. Tzoganakis and J. F. Honek, 2011, Controllable Delivery of Small Molecule Compounds to Targeted Cells Utilizing Carbon Nanotubes. Journal of the American Chemical Society, 133, 6874-6877.
U. Suttisansanee and J. F. Honek, 2011, Bacterial Glyoxalase Enzymes. Seminars in Cell and Developmental Biology, 22, 285-292.
C. L. Myers, P. C. Hang, G. Ng, J. Yuen, and J. F. Honek, 2010, Semi-synthetic Analogues
of Thiostrepton Delimit the Critical Nature of Tail Region Modifications in the Control of Protein Biosynthesis and Antibacterial Activity. Bioorg. Med. Chem., 18 (12), 4231-4237.
J. F. Honek, A. Francq, and A. J. Carty, 2010, Research Spotlight: Bionanotechnology: Small Can Have a Big Impact in the Medical Sciences: a WIN-Win Situation. Part 2. Future Medicinal Chemistry2 (11), 1627-1632.
J. F. Honek, A. Francq, and A. J. Carty, 2010 Research Spotlight: Bionanotechnology: Small Can Have a Big Impact in the Medical Sciences: a WIN-Win Situation. Part 1. Future Medicinal Chemistry2(10), 1515-1522.