Kenichi Yokoyama

Last updated
Kenichi Yokoyama
Alma mater Tokyo Institute of Technology, Massachusetts Institute of Technology
Scientific career
FieldsBiochemistry, Enzymology, Chemical Biology, Natural Product Chemistry
Institutions Duke University School of Medicine
Website https://sites.duke.edu/yokoyamalab/

Kenichi Yokoyama is an enzymologist, chemical biologist, and natural product biochemist originally from Tokyo, Japan. He is an Associate Professor of Biochemistry at Duke University School of Medicine. In 2019, Yokoyama was awarded the Pfizer Award in Enzyme Chemistry from the American Chemical Society.

Contents

Education

Kenichi Yokoyama received both his Bachelor of Science in Chemistry and PhD in Chemistry from the Tokyo Institute of Technology. For his doctoral work, he elucidated the catalytic mechanism of enzymes involved in the biosynthesis of aminoglycoside antibiotics under the guidance of Tadashi Eguchi. [1] From 2008 through 2011, he pursued postdoctoral studies at the Massachusetts Institute of Technology with enzymologist JoAnne Stubbe. Together they collaborated on deciphering the novel features and catalytic mechanism of ribonucleotide reductases, a group of radical-based enzymes that convert ribonucleotides to deoxyribonucleotides, the building blocks of genetic material. [2] In 2011, he began his independent career at Duke University as an Assistant Professor of Biochemistry and Chemistry. In 2019, he was promoted to Associate Professor with tenure.

Research

The Yokoyama lab's research focuses on natural products, the small organic molecules made by living organisms in nature. [3] Those compounds possess a wide range of activities such as antimicrobial and antitumor. Yokoyama's aims are to characterize the biosynthetic pathways of such molecules and to understand the functions of enzymes that are involved in the process. To that end, his group utilizes techniques and knowledge from various fields including enzymology, biochemistry, molecular biology, bioinformatics, structural biology, and organic chemistry. One of the key achievements of the Yokoyama lab was the identification of a cryptic intermediate in the biosynthesis of molybdenum cofactor, an essential cofactor found in virtually all organisms including bacteria and human. [4] The lab also resolved a multidecade-long mystery in the field by revising the catalytic functions of the first two enzymes in the pathway, MoaA and MoaC. [5] Radical S-adenosylmethionine (SAM) enzyme, a superfamily of enzymes that use iron-sulfur clusters to perform diverse chemical transformations, is another focus of Yokoyama's research program. [6]

In 2018, Yokoyama was named one of 44 prominent scientists worldwide moving Biochemistry into the future. [7] In 2019, he was awarded the Pfizer Award in Enzyme Chemistry from the American Chemical Society, became the third faculty member at Duke University to receive this award after Salih Wakil in 1967 and Paul Modrich in 1983, who later received the Nobel Prize in Chemistry in 2015. [8]

Related Research Articles

In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.

In enzymology, a 5-(carboxyamino)imidazole ribonucleotide mutase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Cystathionine beta-lyase</span> Enzyme

Cystathionine beta-lyase, also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction

<span class="mw-page-title-main">Biotin synthase</span> Enzyme

Biotin synthase (BioB) is an enzyme that catalyzes the conversion of dethiobiotin (DTB) to biotin; this is the final step in the biotin biosynthetic pathway. Biotin, also known as vitamin B7, is a cofactor used in carboxylation, decarboxylation, and transcarboxylation reactions in many organisms including humans. Biotin synthase is an S-Adenosylmethionine (SAM) dependent enzyme that employs a radical mechanism to thiolate dethiobiotin, thus converting it to biotin.

In enzymology, a 5-(carboxyamino)imidazole ribonucleotide synthase (EC 6.3.4.18) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">5-Aminoimidazole ribotide</span> Chemical compound

5′-Phosphoribosyl-5-aminoimidazole is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from AIR. It is an intermediate in the adenine pathway and is synthesized from 5′-phosphoribosylformylglycinamidine by AIR synthetase.

<span class="mw-page-title-main">JoAnne Stubbe</span> American chemist

JoAnne Stubbe is an American chemist best known for her work on ribonucleotide reductases, for which she was awarded the National Medal of Science in 2009. In 2017, she retired as a Professor of Chemistry and Biology at the Massachusetts Institute of Technology.

<span class="mw-page-title-main">Phosphoribosylglycinamide formyltransferase</span>

Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2, 2-amino-N-ribosylacetamide 5'-phosphate transformylase, GAR formyltransferase, GAR transformylase, glycinamide ribonucleotide transformylase, GAR TFase, 5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase) is an enzyme with systematic name 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase. This enzyme catalyses the following chemical reaction

Michelle C. Y. Chang is a Professor of Chemistry and Chemical and Biomolecular Engineering at the University of California, Berkeley, and is a recipient of several young scientist awards for her research in biosynthesis of biofuels and pharmaceuticals.

A transition metal oxo complex is a coordination complex containing an oxo ligand. Formally O2-, an oxo ligand can be bound to one or more metal centers, i.e. it can exist as a terminal or (most commonly) as bridging ligands (Fig. 1). Oxo ligands stabilize high oxidation states of a metal. They are also found in several metalloproteins, for example in molybdenum cofactors and in many iron-containing enzymes. One of the earliest synthetic compounds to incorporate an oxo ligand is potassium ferrate (K2FeO4), which was likely prepared by Georg E. Stahl in 1702.

Radical SAM is a designation for a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. rSAMs comprise the largest superfamily of metal-containing enzymes.

2-deoxy-scyllo-inosamine dehydrogenase (SAM-dependent) is an enzyme with systematic name 2-deoxy-scyllo-inosamine:S-adenosyl-L-methionine 1-oxidoreductase. This enzyme catalyses the following chemical reaction

Cyclic pyranopterin monophosphate synthase is an enzyme with systematic name GTP 8,9-lyase . This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">FeMoco</span> Cofactor of nitrogenase

FeMoco (FeMo cofactor) is the primary cofactor of nitrogenase. Nitrogenase is the enzyme that catalyzes the conversion of atmospheric nitrogen molecules N2 into ammonia (NH3) through the process known as nitrogen fixation. Studying FeMoco's role in the reaction mechanism for nitrogen fixation is a potential use case for quantum computers. Even limited quantum computers could enable better simulations of the reaction mechanism.

<span class="mw-page-title-main">Squire Booker</span> American biochemist

Squire Booker is an American biochemist at Penn State University. Booker directs an interdisciplinary chemistry research program related to fields of biochemistry, enzymology, protein chemistry, natural product biosynthesis, and mechanisms of radical dependent enzymes. He is an associate editor for the American Chemical Society Biochemistry Journal, is a Hughes Medical Institute Investigator, and an Eberly Distinguished Chair in Science at Penn State University.

Sarah E. O'Connor is an American molecular biologist working to understand the molecular machinery involved in assembling important plant natural products – vinblastine, morphine, iridoids, secologanin – and how changing the enzymes involved in this pathway lead to diverse analogs. She was a Project Leader at the John Innes Centre in the UK between 2011 and 2019. O'Connor was appointed by the Max Planck Society in 2018 to head the Department of Natural Product Biosynthesis at the Max Planck Institute for Chemical Ecology in Jena, Germany, taking up her role during 2019.

Methylthiotransferases are enzymes of the radical S-adenosyl methionine superfamily. These enzymes catalyze the addition of a methylthio group to various biochemical compounds including tRNA and proteins. Methylthiotransferases are classified into one of four classes based on their substrates and mechanisms. All methylthiotransferases have been shown to contain two Fe-S clusters, one canonical cluster and one auxiliary cluster, that both function in the addition of the methylthio group to the substrate.

Julia A. Kovacs is an American chemist specializing in bioinorganic chemistry. She is professor of chemistry at the University of Washington. Her research involves synthesizing small-molecule mimics of the active sites of metalloproteins, in order to investigate how cysteinates influence the function of non-heme iron enzymes, and the mechanism of the oxygen-evolving complex (OEC).

<span class="mw-page-title-main">Non-heme iron protein</span>

In biochemistry, non-heme iron proteins describe families of enzymes that utilize iron at the active site but lack heme cofactors. Iron-sulfur proteins, including those that are enzymes, are not included in this definition.

R. David Britt is the Winston Ko Chair and Distinguished Professor of Chemistry at the University of California, Davis. Britt uses electron paramagnetic resonance (EPR) spectroscopy to study metalloenzymes and enzymes containing organic radicals in their active sites. Britt is the recipient of multiple awards for his research, including the Bioinorganic Chemistry Award in 2019 and the Bruker Prize in 2015 from the Royal Society of Chemistry. He has received a Gold Medal from the International EPR Society (2014), and the Zavoisky Award from the Kazan Scientific Center of the Russian Academy of Sciences (2018). He is a Fellow of the American Association for the Advancement of Science and of the Royal Society of Chemistry.

References

  1. ↑ Yokoyama, Kenichi; Numakura, Mario; Kudo, Fumitaka; Ohmori, Daijiro; Eguchi, Tadashi (2007-12-01). "Characterization and Mechanistic Study of a Radical SAM Dehydrogenase in the Biosynthesis of Butirosin". Journal of the American Chemical Society. 129 (49): 15147–15155. doi:10.1021/ja072481t. ISSN   0002-7863. PMID   18001019.
  2. ↑ Yokoyama, Kenichi; Smith, Albert A.; Corzilius, Björn; Griffin, Robert G.; Stubbe, JoAnne (2011-11-16). "Equilibration of Tyrosyl Radicals (Y356•, Y731•, Y730•) in the Radical Propagation Pathway of the Escherichia coli Class Ia Ribonucleotide Reductase". Journal of the American Chemical Society. 133 (45): 18420–18432. doi:10.1021/ja207455k. ISSN   0002-7863. PMC   3236566 . PMID   21967342.
  3. ↑ "Yokoyama Lab | The frontier of enzymology and natural product biochemistry" . Retrieved 2022-03-03.
  4. ↑ Hover, Bradley M.; Loksztejn, Anna; Ribeiro, Anthony A.; Yokoyama, Kenichi (2013-05-08). "Identification of a Cyclic Nucleotide as a Cryptic Intermediate in Molybdenum Cofactor Biosynthesis". Journal of the American Chemical Society. 135 (18): 7019–7032. doi:10.1021/ja401781t. ISSN   0002-7863. PMC   3777439 . PMID   23627491.
  5. ↑ Yokoyama, Kenichi; Li, Di; Pang, Haoran (2021-12-13). "Resolving the Multidecade-Long Mystery in MoaA Radical SAM Enzyme Reveals New Opportunities to Tackle Human Health Problems". ACS Bio & Med Chem Au. doi: 10.1021/acsbiomedchemau.1c00046 . PMC   9026282 . PMID   35480226. S2CID   245212943.
  6. ↑ "Radical SAM enzymology | Yokoyama Lab" . Retrieved 2022-03-03.
  7. ↑ Schepartz, Alanna (2018-01-09). "Introducing the "Future of Biochemistry" Special Issue". Biochemistry. 57 (1): 1–8. doi: 10.1021/acs.biochem.7b01259 . ISSN   0006-2960. PMID   29310439.
  8. ↑ "Ken Yokoyama, PhD wins Pfizer Award | Duke Department of Biochemistry". www.biochem.duke.edu. Retrieved 2022-03-03.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.