Article
Biochemistry & Molecular Biology
Peter D. Giang, Luke R. Churchman, Jeanette E. Stok, Rochelle M. Soo, James J. De Voss
Summary: A study found that Rhodococcus globerulus (R. globerulus) isolated from soil beneath Eucalyptus sp. can thrive on mono-terpenes such as 1,8-cineole, p-cymene and (R)- and (S)-limonene as its sole sources of carbon and energy. The research revealed a novel cytochrome P450 (CYP108N12) in R. globerulus which may be responsible for initiating the biodegradation of structurally similar monoterpene compounds. This finding suggests that CYP108N12 has potential as a biocatalyst with specific hydroxylation capabilities.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Roelant Hilgers, Sin Yong Teng, Anamarija Bris, Aleksandr Y. Pereverzev, Paul White, Jeroen J. Jansen, Jana Roithova
Summary: This study introduces a simple and rapid method for determining enantioselectivities based on mass spectrometry. By using ion mobility separation and delayed reactant labeling experiments, the method can link mass spectra with reaction kinetics to predict the enantioselectivity of the overall reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Xin Nie, Zihan Yan, Sergei Ivlev, Eric Meggers
Summary: Enantioselective C(sp(3))-H aminations provide an efficient access to nonracemic chiral amines. This work describes the catalytic asymmetric synthesis of chiral 1,2,5-thiadiazolidine-1,1-dioxides using a recently introduced simple chiral ruthenium bis(oxazoline) complex, achieving high yields and enantioselectivities. Mechanistic experiments confirmed a stepwise mechanism and demonstrated that the cyclic sulfamide products are suitable for the synthesis of chiral vicinal diamines.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jie Chen, Sheng Dong, Wenhan Fang, Yiping Jiang, Zhifeng Chen, Xiangquan Qin, Cong Wang, Haifeng Zhou, Longyi Jin, Yingang Feng, Binju Wang, Zhiqi Cong
Summary: We report the selective hydroxylation of alkylbenzenes using an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). By combining different P450BM3 variants with DFSMs, more than half of all possible hydroxylated products were obtained from each substrate with high regioselectivity (>99%), enantioselectivity (>99% ee), and high total turnover numbers (up to 80963). Synergistic effects between exogenous DFSMs and the protein environment controlled the regio- and enantioselectivity, as revealed by crystal structure analysis, molecular dynamic simulations, and theoretical calculations. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Kazuto Suzuki, Joshua Kyle Stanfield, Keita Omura, Yuma Shisaka, Shinya Ariyasu, Chie Kasai, Yuichiro Aiba, Hiroshi Sugimoto, Osami Shoji
Summary: Catching the structure of cytochrome P450 enzymes in flagrante is crucial for the development of P450 biocatalysts. We report the crystal structure of P450BM3 mimicking the state in the precise moment preceding epoxidation, which is in perfect agreement with the experimentally observed stereoselectivity. This method serves as a powerful tool for predicting and modelling the stereoselectivity of P450 reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Laurentijn Tilleman, Kaat Rubben, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerburgh
Summary: This study tested the effectiveness of Targeted Locus Amplification (TLA) combined with Illumina or Nanopore sequencing in accurate genotyping and phasing of pharmacogenes. The results showed limited nucleotide mapping on target and incomplete coverage of genes with both sequencing methods. However, the optimized primer pair for the CYP2D6 gene in the Nanopore dataset resulted in correct haplotypes, indicating the potential reliability of this method with patient-specific primer design and optimization.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Lulu Ni, Ping Miao, Jian Jiang, Fang Wan, Jiangan Li, Min Ai, Lingzhong Kong, Su Tu
Summary: This study found that Glycyrrhiza promotes the metabolism of toxic components of Aconitum by upregulating the expression of CYP3A, reducing the content of heart failure-related markers, and improving the myocardial energy metabolism disorder, thus alleviating the development of congestive heart failure.
Review
Chemistry, Multidisciplinary
Johannes Grosskopf, Thorsten Bach
Summary: Upon irradiation with a suitable chiral catalyst, racemic compounds can be converted into enantiopure compounds through a process called photochemical deracemization. This review comprehensively covers the research and current developments in this field, discussing the reactions and mechanistic details underlying the presented reaction. Photochemical deracemization offers a unique opportunity to directly obtain enantiopure compounds from racemates, and short-lived intermediates play a key role in determining the enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Thomas Lautier, Derek J. Smith, Lay Kien Yang, Xixian Chen, Congqiang Zhang, Gilles Truan, Nic D. Lindley
Summary: Molecular biodiversity is a result of enzymatic regioselectivities in branched metabolic pathways. Metabolites with internal structural symmetry, such as beta-carotene, offer identical extremities to enzymes, presenting additional complexity. This study investigates the unique monohydroxylase activity of CYP97H1, the only monohydroxylase among CYP97 dihydroxylases, in a substrate with two identical sites for hydroxylation. It is found that the N-terminal globular domain of CYP97H1, which contains a hydrophobic patch at the entrance of the substrate channel, is responsible for this regioselectivity.
Article
Chemistry, Multidisciplinary
Alecia R. Gee, Isobella S. J. Stone, Tegan P. Stockdale, Tara L. Pukala, James J. De Voss, Stephen G. Bell
Summary: We have achieved efficient oxidation reactions on unactivated carbon-hydrogen bonds by modifying the enzyme structure.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Lara E. Zetzsche, Suman Chakrabarty, Alison R. H. Narayan
Summary: This study optimized a whole-cell biocatalytic platform for the synthesis of biaryl molecules in yeast through recombinant production of the fungal P450 KtnC. Moreover, engineering redox self-sufficient fusion enzymes further enhanced the efficiency of the system. This provides a platform for engineering currently underexplored fungal P450s into selective biocatalysts for the synthesis of complex biaryl compounds.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Aminah Alchakee, Munazza Ahmed, Leen Eldohaji, Hamid Alhaj, Maha Saber-Ayad
Summary: The review focuses on cytochrome P450 enzymes and their association with the metabolism of psychotropic medications, variations among different populations, impact on neurotransmitters, and the influence of non-genetic factors. It also discusses the association between adverse effects of psychiatric medications and human leukocytic antigen genotypes. The importance of pharmacogenetics implementation in psychiatry clinics is emphasized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Dairy & Animal Science
Kanami Watanabe, Mitsuki Kondo, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka
Summary: Our study compares genomic data from 12 mammalian species and investigates a specific genetic loss and duplication in elephants. We found that elephant CYP1-4 genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, forming a unique cluster. However, CYP2E and CYP4A in elephants have decayed to a state of genetic dysfunction. These findings provide new insights into elephant xenobiotic metabolism.
Article
Biochemistry & Molecular Biology
Maria Carolina Stipp, Juliana Danna Kulik, Claudia Rita Corso, Claudia Martins Galindo, Eliana Rezende Adami, Alberto Goncalves Evangelista, Fernando Bittencourt Luciano, Sheila Maria Brochado Winnischofer, Silvia Maria Suter Correia Cadena, Guilherme Lanzi Sassaki, Alexandra Acco
Summary: The soluble fraction of polysaccharides from cabernet franc red wine (SFP) has been found to have antitumoral effects by modulating the immune system. This study confirms that SFP can regulate CYPs both in vitro and in vivo. The results suggest that SFP inhibits CYPs likely through its immunoinflammatory actions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Courtney M. Krest, Alexey Silakov, Jonathan Rittle, Timothy H. Yosca, Elizabeth L. Onderko, Julio C. Calixto, Michael T. Green
Article
Chemistry, Multidisciplinary
Timothy H. Yosca, Matthew C. Langston, Courtney M. Krest, Elizabeth L. Onderko, Tyler L. Grove, Jovan Livada, Michael T. Green
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2016)
Article
Chemistry, Multidisciplinary
Ethan A. Hill, Andrew C. Weitz, Elizabeth Onderko, Adrian Romero-Rivera, Yisong Guo, Marcel Swart, Emile L. Bominaar, Michael T. Green, Michael P. Hendrich, David C. Lacy, A. S. Borovik
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2016)
Article
Chemistry, Multidisciplinary
Elizabeth L. Onderko, Alexey Silakov, Timothy H. Yosca, Michael T. Green
Article
Chemistry, Multidisciplinary
Timothy H. Yosca, Rachel K. Behan, Courtney M. Krest, Elizabeth L. Onderko, Matthew C. Langston, Michael T. Green
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Multidisciplinary Sciences
Timothy H. Yosca, Jonathan Rittle, Courtney M. Krest, Elizabeth L. Onderko, Alexey Silakov, Julio C. Calixto, Rachel K. Behan, Michael T. Green
Article
Microbiology
Lina J. Bird, Zheng Wang, Anthony P. Malanoski, Elizabeth L. Onderko, Brandy J. Johnson, Martin H. Moore, Daniel A. Phillips, Brandon J. Chu, J. Fitzpatrick Doyle, Brian J. Eddie, Sarah M. Glaven
FRONTIERS IN MICROBIOLOGY
(2018)
Article
Materials Science, Multidisciplinary
Lina J. Bird, Elizabeth L. Onderko, Daniel A. Phillips, Rebecca L. Mickol, Anthony P. Malanoski, Matthew D. Yates, Brian J. Eddie, Sarah M. Glaven
MRS COMMUNICATIONS
(2019)
Article
Biochemical Research Methods
Adam Meyer, Ishtiaq Saaem, Adam Silverman, Vanessa A. Varaljay, Rebecca Mickol, Steven Blum, Alexander V. Tobias, Nathan D. Schwalm, Wais Mojadedi, Elizabeth Onderko, Cassandra Bristol, Shangtao Liu, Katelin Pratt, Arturo Casini, Raissa Eluere, Felix Moser, Carrie Drake, Maneesh Gupta, Nancy Kelley-Loughnane, Julius P. Lucks, Katherine L. Akingbade, Matthew P. Lux, Sarah Glaven, Wendy Crookes-Goodson, Michael C. Jewett, D. Benjamin Gordon, Christopher A. Voigt
ACS SYNTHETIC BIOLOGY
(2019)
Article
Materials Science, Multidisciplinary
Patrick B. Dennis, Elizabeth L. Onderko, Joseph M. Slocik, Lina J. Bird, Daniel A. Phillips, Wendy J. Crookes-Goodson, Sarah M. Glaven
Article
Biochemistry & Molecular Biology
Matthew D. Yates, Lina J. Bird, Brian J. Eddie, Elizabeth L. Onderko, Christopher A. Voigt, Sarah M. Glaven
Summary: This study demonstrates nanoscale chronoamperometry and cyclic voltammetry of various electroactive bacteria in a three-electrode reactor system, paving the way for the development of miniaturized and potentially high-throughput bioelectrochemical platforms.
BIOELECTROCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Syam Sundar Neti, Bo Wang, David F. Iwig, Elizabeth L. Onderko, Squire J. Booker
Summary: Fluoromethyl, difluoromethyl, and trifluoromethyl groups are important in pharmaceuticals and agrochemicals for their roles in efficacy and metabolic stability. Late-stage incorporation of fluorine-containing atoms in molecules has become a significant field in organic and medicinal chemistry, as well as synthetic biology. This study presents a novel fluoromethylating agent, FMeTeSAM, which is structurally and chemically similar to S-adenosyl-L-methionine (SAM) and supports efficient transfer of fluoromethyl groups to oxygen, nitrogen, sulfur, and some carbon nucleophiles. FMeTeSAM is also applied in the fluoromethylation of precursors to oxaline and daunorubicin, two natural products with antitumor properties.
ACS CENTRAL SCIENCE
(2023)
Article
Microbiology
Brian J. Eddie, Anthony P. Malanoski, Elizabeth L. Onderko, Daniel A. Phillips, Sarah M. Glaven
Summary: Marinobacter atlanticus produces small amounts of electrical current on electrodes, which is enhanced by the addition of redox mediators; RNA-sequencing revealed increased expression of genes for molybdate transport and type VI secretion system in cells grown at current-producing potentials.
Article
Energy & Fuels
Elizabeth L. Onderko, Daniel A. Phillips, Brian J. Eddie, Matthew D. Yates, Zheng Wang, Leonard M. Tender, Sarah M. Glaven
FRONTIERS IN ENERGY RESEARCH
(2019)