Article
Pharmacology & Pharmacy
Line Skute Braten, Tore Haslemo, Marin M. Jukic, Maxim Ivanov, Magnus Ingelman-Sundberg, Espen Molden, Marianne Kristiansen Kringen
Summary: Escitalopram, a commonly used antidepressant drug, shows substantial interindividual variation in clinical response, which can be attributed to the polymorphic nature of the CYP2C19 gene. A novel CYP2C-haplotype associated with ultrarapid metabolism of escitalopram was identified in this study.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Gustavo Perez Ortiz, John D. Sidda, Emmanuel L. C. de los Santos, Catherine B. Hubert, Sarah M. Barry
Summary: The antimycobacterial peptides rufomycins exhibit antibiotic activity due to oxidative tailoring of the cyclic peptide. Cytochrome P450s RufS and RufM play roles in regioselective epoxidation and alkyl oxidation, creating a complex product profile dependent on redox partner availability. Additionally, in vitro one pot conversion of rufomycin B to rufomycin C has been successfully demonstrated.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Sebastian Adam, Dazhong Zheng, Andreas Klein, Carsten Volz, William Mullen, Sally L. Shirran, Brian O. Smith, Olga V. Kalinina, Rolf Mueller, Jesko Koehnke
Summary: In this study, we identified three proteins (CgnB, CgnC, and CgnE) responsible for the production of the tetracyclic crocagin core. Crystal structures of two homologues (CgnB and CgnE) provided insights into their functions. We also discovered the roles of CgnD and CgnL in the liberation and modification of the crocagin core, respectively, and proposed a biosynthetic scheme. Bioinformatic analyses further revealed potential pathways for the synthesis of structurally diverse peptide-derived pyrroloindoline alkaloids.
Article
Multidisciplinary Sciences
Sumiko Ohnami, Akane Naruoka, Mitsuhiro Isaka, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Ai Sakai, Keiichi Ohshima, Keiichi Hatakeyama, Kouji Maruyama, Yasuhisa Ohde, Hirotsugu Kenmotsu, Toshiaki Takahashi, Yasuto Akiyama, Takeshi Nagashima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi
Summary: The differences in genetic susceptibility to lung adenocarcinoma and squamous cell carcinoma are still not clear. Researchers developed a gene sequencing panel to detect germline variants in these two types of cancer. The study found that certain gene variants were associated with an increased risk of squamous cell carcinoma, while whole-gene deletion was associated with adenocarcinoma.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
He Liu, Zixia Hu, Ningning Han, Yi Yang, Guode Zhao, Mengdie Su, Yue Zhang, Weiwei Li, Ying Peng, Jiang Zheng
Summary: The study aimed to investigate the metabolic activation of MTX and its possible correlation with cytotoxicity. An oxidative metabolite (M1) and a GSH conjugate (M2) were observed in S9 fraction incubations and rat primary hepatocyte culture after MTX exposure. M1 and M2 were also detected in the bile of MTX-treated rats. CYP2A6 was found to be the dominant enzyme responsible for the oxidation of MTX. Inhibition of CYP2A6 and sulfotransferase significantly decreased the formation of M2. Pretreatment of primary hepatocytes with inhibitors reduced the susceptibility to MTX-induced cytotoxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Xiaolu Chen, Dongru Sun, Lanping Gao, Yufen Zhao, Sam P. de Visser, Yong Wang
Summary: DFT calculations reveal that the iodine of cobalt(ii)-iodylarene complexes acts as a directing group via halogen bonding interaction to substrates. A transient 3c-4e bond is formed during oxidation reactions to decrease the activation energy by electron delocalization. Dehydrogenation of dihydroantharacene proceeds via a novel concerted hydride transfer/proton transfer mechanism.
CHEMICAL COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Melina Lopez, Pedro F. Malacarne, Anna Gajos-Draus, Xinxin Ding, Andreas Daiber, Jon O. Lundberg, Stefan Offermanns, Ralf P. Brandes, Flavia Rezende
Summary: The study suggests that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates, while ALDH2 plays an important role in activating organic nitrates.
BRITISH JOURNAL OF PHARMACOLOGY
(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
Multidisciplinary Sciences
Chunshun Li, Yifei Hu, Xiaohua Wu, Spencer D. Stumpf, Yunci Qi, John M. D'Alessandro, Keshav K. Nepal, Ariel M. Sarotti, Shugeng Cao, Joshua A. V. Blodgett
Summary: Rare actinomycetes are a valuable but underexploited source of bioactive compounds. In this study, a targeted metabologenomic approach was used to identify piperazyl compounds in the rare actinomycete Lentzea flaviverrucosa DSM 44664. The discovery of two dimeric biaryl-cyclohexapeptides, petrichorins A and B, with potent anticancer activity, highlights the potential of rare actinomycetes for drug discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Biochemistry & Molecular Biology
F. Peter Guengerich
Summary: The paper introduces the concept of cytochrome b(5) as an auxiliary protein facilitating cytochrome P450 reactions, providing important insights for future research.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Chemistry, Medicinal
Soudeh Bahramian Nasab, Ahmad Homaei, Roberto Fernandez-Lafuente, Jon Del Arco, Jesus Fernandez-Lucas
Summary: The use of marine enzymes as catalysts for biotechnological applications is a hot topic. In this study, a liver NADPH-dependent cytochrome P450 reductase (CPR) from the marine fish Liza klunzingeri (LkCPR) was isolated, purified and biochemically characterized. LkCPR showed remarkable catalytic features, such as a wide range of pH and temperature stability, high catalytic activity, and highest thermostability among reported CPRs. These findings suggest that LkCPR has great potential as a biocatalyst.
Article
Environmental Sciences
Xiaoxia Yang, Xuemei Zhang, Xiao Shu, Jiuping Gong, Junying Yang, Biquan Li, Junjie Lin, Yong Chai, Jianfei Liu
Summary: This study found that polyethylene (PE) microplastics (MPs) smaller than 5 mm exert toxic effects on earthworms, with concentrations exceeding 2.5 g/kg causing significant changes in metabolic enzyme activities and metabolites. The toxicity of PE MPs to earthworms is likely associated with neurotoxicity, oxidative damage, decreased detoxification capacity, energy metabolism imbalance, and impaired amino acid and purine metabolism due to bioaccumulation. The findings of this study contribute to a better understanding of the molecular toxicity mechanisms of PE MPs and the ecological risks they pose.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Review
Microbiology
James B. Y. H. Behrendorff
Summary: Cytochrome P450 enzymes, known for their ability to insert oxygen into a wide range of substrates, can also perform reductive reactions under hypoxic conditions, contributing to the dehalogenation and denitration of environmental pollutants. This enzyme activity, first discovered in human pharmacology, has been observed in various organisms.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eerappa Rajakumara, Dubey Saniya, Priyanka Bajaj, Rajanna Rajeshwari, Jyotsnendu Giri, Mehdi D. D. Davari
Summary: Cytochrome P450s are important enzymes for the oxidative transformation of organic substrates. Factors such as protein structure, substrate binding, and redox potential modulation play a crucial role in determining the catalytic properties and selectivity of P450s. Understanding these factors is increasingly important in the fields of synthetic biology and biotechnology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Hongming Song, Chuankui Wei, Wu Yang, Zhaohe Niu, Mingkai Gong, Haiyan Hu, Haibo Wang
Summary: This study assessed the effect of alpinetin on the activity of cytochrome P450 enzymes (CYP450s) and found that alpinetin inhibited the activity of CYP3A4, 2C9, and 2E1, suggesting potential drug interactions.
PHARMACEUTICAL BIOLOGY
(2022)
Correction
Chemistry, Medicinal
M. E. Kavanagh, J. L. Gray, S. H. Gilbert, A. G. Coyne, K. J. McLean, H. J. Davis, A. W. Munro, C. Abell
Article
Biochemistry & Molecular Biology
Jude T. Chenge, Le Van Duyet, Shalini Swami, Kirsty J. McLean, Madeline E. Kavanagh, Anthony G. Coyne, Stephen E. J. Rigby, Myles R. Cheesman, Hazel M. Girvan, Colin W. Levy, Bernd Rupp, Jens P. von Kries, Chris Abell, David Leys, Andrew W. Munro
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Ismail M. Taban, Hosam E. A. E. Elshihawy, Beyza Torun, Benedetta Zucchini, Clare J. Williamson, Dania Altuwairigi, Adeline S. T. Ngu, Kirsty J. McLean, Colin W. Leyy, Sakshi Sood, Leonardo B. Marino, Andrew W. Munro, Luiz Pedro S. de Caryalho, Claire Simone
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Spectroscopy
Yilin Liu, Kirsty J. McLean, Andrew W. Munro, James R. Kincaid
JOURNAL OF RAMAN SPECTROSCOPY
(2018)
Review
Biochemistry & Molecular Biology
Andrew W. Munro, Kirsty J. McLean, Job L. Grant, Thomas M. Makris
BIOCHEMICAL SOCIETY TRANSACTIONS
(2018)
Article
Biochemistry & Molecular Biology
Hend A. A. Abd El-Wahab, Mauro Accietto, Leonardo B. Marino, Kirsty J. McLean, Colin W. Levy, Hamdy M. Abdel-Rahman, Mahmoud A. El-Gendy, Andrew W. Munro, Ahmed S. Aboraia, Claire Simons
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Physical
Carlos G. Acevedo-Rocha, Charles G. Gamble, Richard Lonsdale, Aitao Li, Nathalie Nett, Sabrina Hoebenreich, Julia B. Lingnau, Cornelia Wirtz, Christophe Fares, Heike Hinrichs, Alfred Deege, Adrian J. Mulholland, Yuval Nov, David Leys, Kirsty J. McLean, Andrew W. Munro, Manfred T. Reetz
Article
Biochemistry & Molecular Biology
Hazel M. Girvan, Harshwardhan Poddar, Kirsty J. McLean, David R. Nelson, Katherine A. Hollywood, Colin W. Levy, David Leys, Andrew W. Munro
JOURNAL OF INORGANIC BIOCHEMISTRY
(2018)
Editorial Material
Biochemistry & Molecular Biology
Andrew W. Munro
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Safaa M. Kishk, Kirsty J. McLean, Sakshi Sood, Mohamed A. Helal, Mohamed S. Gomaa, Ismail Salama, Samia M. Mostafa, Luiz Pedro S. de Carvalho, Andrew W. Munro, Claire Simons
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Laura N. Jeffreys, Harshwardhan Poddar, Marina Golovanova, Colin W. Levy, Hazel M. Girvan, Kirsty J. McLean, Michael W. Voice, David Leys, Andrew W. Munro
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Multidisciplinary
Safaa M. Kishk, Kirsty J. McLean, Sakshi Sood, Darren Smith, Jack W. D. Evans, Mohamed A. Helal, Mohamed S. Gomaa, Ismail Salama, Samia M. Mostafa, Luiz Pedro S. de Carvalho, Colin W. Levy, Andrew W. Munro, Claire Simons
Article
Chemistry, Medicinal
Sarah Matthews, Kamila J. Pacholarz, Aidan P. France, Thomas A. Jowitt, Sam Hay, Perdita Barran, Andrew W. Munro
ACS INFECTIOUS DISEASES
(2019)
Article
Chemistry, Medicinal
Sunnia Rajput, Kirsty J. McLean, Harshwardhan Poddar, Irwin R. Selvam, Gayathri Nagalingam, James A. Triccas, Colin W. Levy, Andrew W. Munro, Craig A. Hutton
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Meeting Abstract
Biochemistry & Molecular Biology
A. Munro, K. McLean, J. Belcher, S. Matthews, H. Girvan, K. Tee, H. Poddar, A. Andrews, D. Leys, M. Hans, M. van den Berg, L. Jeffreys