Article
Chemistry, Multidisciplinary
Jessica A. Gable, Sarvind Tripathi, Thomas L. Poulos
Summary: A characteristic feature of cytochromes P450 is the generation of an intense absorption band at 450 nm when the ferrous heme iron forms a complex with carbon monoxide. The P450-to-P420 change is primarily due to an opening and disordering of the substrate binding pocket, rather than ligand displacement or swapping.
Article
Agriculture, Multidisciplinary
Xiao Yan Zhai, Zhao Jie Chen, Jintong Liu, Nan Zhang, Hong Yang
Summary: In this study, a new cytochrome P450 gene, CYP76C6, was discovered in rice, which plays a critical role in accelerating the degradation of isoproturon (IPU). Overexpression of CYP76C6 improved rice growth, attenuated IPU-induced cellular damage, and repressed IPU accumulation. The study provides insights into the mechanism of IPU decay in rice crops and its potential application in reducing environmental risks and ensuring food safety and human health.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Agriculture, Multidisciplinary
Xueke Gao, Xiangzhen Zhu, Chuanpeng Wang, Li Wang, Kaixin Zhang, Dongyang Li, Jichao Ji, Lin Niu, Junyu Luo, Jinjie Cui
Summary: This study characterized AgoCYP6CY19, a CYP gene in Aphis gossypii, and found that its expression is related to developmental stages and host specialization. Silencing AgoCYP6CY19 increased mortality and reduced fecundity in aphids. Additionally, AgoCYP6CY19 was induced by certain plant substances. These findings highlight the importance of AgoCYP6CY19 in detoxification and metabolism processes.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Meredith R. McGuire, Peter J. Espenshade
Summary: Progesterone Receptor Membrane Component 1 (PGRMC1) is a heme-binding protein involved in various cellular and tissue functions. However, the underlying mechanisms of PGRMC1 in these biological aspects remain largely unknown. This review provides an overview of the literature on PGRMC1, highlighting supported information and areas for further investigation. The central role of PGRMC1 in cytochrome P450 activity is extensively discussed, and a speculative model is proposed regarding its function as a heme chaperone. By identifying knowledge gaps, this review aims to inspire a better understanding of this enigmatic protein.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Physiology
Xingxing Yuan, Han Li, Xianru Guo, He Jiang, Qi Zhang, Lijuan Zhang, Gaoping Wang, Weizheng Li, Man Zhao
Summary: In this study, two novel CYP450 genes, CYP6CV1 and CYP6AB51, were identified and characterized in C. punctiferalis. The expression patterns of these genes in different developmental stages and tissues were studied using qRT-PCR technology. The results showed that the expression levels of CYP6CV1 and CYP6AB51 were significantly induced by the three insecticides, and the mortality rates of the larvae increased when treated with the insecticides. The findings suggest that CYP6CV1 and CYP6AB51 play crucial roles in the detoxification of the insecticides in C. punctiferalis.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Liu-Qiang Wang, Shuang-Shuang Wen, Rui Wang, Chao Wang, Bei Gao, Meng-Zhu Lu
Summary: The study reveals that PagWOX11/12a enhances salt tolerance in poplar trees by modulating ROS scavenging to reduce the accumulation of H2O2 under salt stress.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Masayuki Karasawa, Kai Yonemura, Joshua Kyle Stanfield, Kazuto Suzuki, Osami Shoji
Summary: The study shows that the cellular uptake of external additives by Escherichia coli whole-cell biocatalysts can be significantly improved through the use of an OmpF loop deletion mutant and decoy molecules, leading to increased benzene biotransformation yield and enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Jared Goldstone, David C. Lamb, Steven L. Kelly, Galina I. Lepesheva, John J. Stegeman
Summary: This study investigates the molecular adaptation of deep-sea proteins to high hydrostatic pressure using cytochrome P450 enzymes from Coryphaenoides armatus. The results reveal the ability of Coryphaenoides armatus CYP51 enzyme to bind and catalyze the metabolism of its substrate, as well as amino acid substitutions and novel internal cavities that may be related to deep-sea adaptation. This research contributes to our understanding of protein functional adaptation in extreme environments.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Anja Greule, Thierry Izore, Daniel Machell, Mathias H. Hansen, Melanie Schoppet, James J. De Voss, Louise K. Charkoudian, Ralf B. Schittenhelm, Jeffrey R. Harmer, Max J. Cryle
Summary: Cytochrome P450 enzymes are enzymes that can perform oxidative reactions using heme. However, some of these enzymes can be damaged by oxidation, leading to decreased enzyme activity. Research has shown that the heme orientation in the active site of certain cytochrome P450 enzymes may contribute to this oxidative damage.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hebatalla Mohamed, Stella A. Child, John B. Bruning, Stephen G. Bell
Summary: Members of the CYP51 family of cytochrome P450 enzymes, including CYP51 from Mycobacterium marinum and Mycobacterium tuberculosis, were studied to determine their functional conservation. The enzymes displayed differences in heme spin state and ligand binding, indicating structural differences. Both enzymes were able to oxidatively demethylate lanosterol, but had different binding properties compared to other bacterial and eukaryotic species.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Baodong Hu, Xinrui Zhao, Endao Wang, Jingwen Zhou, Jianghua Li, Jian Chen, Guocheng Du
Summary: Natural products are structurally diverse molecules with a wide range of biological activities. Cytochrome P450 enzymes are involved in the biosynthesis of many natural products and recent research has provided new insights for their application in the biosynthesis of natural products.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hebatalla Mohamed, Amna Ghith, Stephen G. Bell
Summary: The cytochrome P450 superfamily of enzymes can catalyse oxidation reactions and their heme and active site environment can be studied using UV-visible absorbance spectroscopy. The binding of imidazole and pyridine-based ligands to different forms of bacterial cytochrome P450 enzymes was evaluated using this technique. The majority of ligands interacted with the heme as expected, but differences in heme environment were observed across enzyme/ligand combinations.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Qiuhua Liu, Junhao Gao, Yusheng Zhang, Xin Liu, Xi Zhang, Qin Lin, Wennan Zeng, Zaichun Zhou
Summary: In this study, a trans-ortho-di-strapped zinc porphyrin with dome-like deformation was synthesized by thermodynamically controlling the formation of trans- precursor of porphyrinogen. Its single-crystal structure revealed the unique features of creating two secondary coordination sphere (SCS) bulks, maintaining a unique dome deformation, and making atomic out-of-plane deviation. This metallic complex integrates at least three key features, making it an ideal heme analog.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Physical
Ying Wang, Baichun Hu, Yupeng Zhang, Dong Wang, Zhaohu Luo, Jian Wang, Fengjiao Zhang
Summary: The study found that the selectivity between CYP1A1 and CYP1B1 mainly depends on the sustainability of pi-pi stacking interactions with phenylalanine residues. Structural flexibility of protein domains orchestrates this interaction, determining binding selectivity. Modification of naphthoflavone compounds to satisfy pi-pi stacking interactions of key phenylalanine residues in CYP1B1 could improve inhibitory selectivity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Sonia J. Parikh, Sumit Kamat, Margaret Phillips, Samuel P. Boyson, Thomas Yarbrough, Dylan Davie, Qinghai Zhang, Karen C. Glass, Manish B. Shah
Summary: CYP2C9 enzyme plays a crucial role in metabolizing clinical drugs, and the variant CYP2C9*8 found in individuals of African ancestry affects the clearance of certain drug substrates. The structural and solution characterization of CYP2C9*8 provides valuable insights into the differences in drug binding compared to the wild-type enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ruijie K. Zhang, Kai Chen, Xiongyi Huang, Lena Wohlschlager, Hans Renata, Frances H. Arnold
Article
Biochemistry & Molecular Biology
Ella J. Watkins, Patrick J. Almhjell, Frances H. Arnold
Article
Chemistry, Multidisciplinary
Madeleine S. Beasley, Margaret A. Lumley, Tesia D. Janicki, Rebeca L. Fernandez, Lydia H. Manger, Trisha Tucholski, Nicole C. Thomas, Lauren D. Whitmire, Andrea Lawson, Andrew R. Buller
JOURNAL OF CHEMICAL EDUCATION
(2020)
Review
Chemistry, Physical
Kai Chen, Frances H. Arnold
Article
Biochemistry & Molecular Biology
Prasanth Kumar, Anthony Meza, Jonathan M. Ellis, Grace A. Carlson, Craig A. Bingman, Andrew R. Buller
Summary: L-Threonine transaldolases (LTTAs) are a class of enzymes dependent on PLP, responsible for synthesizing diverse beta-hydroxy amino acids. ObiH, an essential LTTA for the biosynthesis of the beta-lactone natural product obafluorin, has been studied to understand its catalytic mechanism and structural features. The data explain the unique reactivity of LTTA enzymes and provide a basis for future engineering and mechanistic analysis.
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lydia J. Perkins, Brian R. Weaver, Andrew R. Buller, Judith N. Burstyn
Summary: This study introduces a novel method for biosynthesizing cobalt protoporphyrin IX (CoPPIX) using Escherichia coli BL21(DE3) under specific growth conditions. The newly synthesized CoPPIX has been successfully incorporated into multiple proteins, providing a new pathway for the synthesis of nonnatural cofactors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Ella J. Watkins-Dulaney, Noah P. Dunham, Sabine Straathof, Soma Turi, Frances H. Arnold, Andrew R. Buller
Summary: The engineered TrpB enzyme can catalyze the asymmetric alkylation of ketones, addressing a significant challenge in synthetic chemistry. Through directed evolution, high selectivity is achieved in the alkylation of propiophenone and 2-fluoroacetophenone. Control over stereochemistry at the new chiral center is demonstrated, showing potential for efficient synthesis of non-canonical prolines and other chirally dense nitrogen heterocycles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Jonathan M. Ellis, Meghan E. Campbell, Prasanth Kumar, Eric P. Geunes, Craig A. Bingman, Andrew R. Buller
Summary: Enantioselective C-C bond-forming reactions are underdeveloped in biocatalysis. This study presents an engineered decarboxylative aldolase enzyme that facilitates the synthesis of non-standard gamma-hydroxy amino acids. The enzyme shows improved activity through directed evolution and engineering, and demonstrates high efficiency in whole-cell biocatalysis reactions.
Article
Chemistry, Multidisciplinary
Tyler J. Doyon, Andrew R. Buller
Summary: Deuterated amino acids play important roles in drug development, nuclear magnetic resonance (NMR) analysis, and enzyme mechanism studies. Enzymatic methods for introducing deuterium offer improved efficiency compared to small molecule-based methods. However, achieving site selectivity for enzyme-mediated deuteration remains a challenge.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Anthony Meza, Meghan E. Campbell, Anna Zmich, Sierra A. Thein, Abbigail M. Grieger, Matthew J. McGill, Patrick H. Willoughby, Andrew R. Buller
Summary: Multi-enzyme biocatalytic cascades provide a practical route for the synthesis of complex bioactive molecules. In this study, a chemoenzymatic platform was developed to convert aryl epoxides into alpha-aryl aldehydes and then further react with L-threonine to produce beta-hydroxy-alpha-amino acids. The whole-cell biocatalyst, produced through co-expression of two enzymes in E. coli, demonstrated the ability to synthesize a variety of stereopure non-standard amino acids on a gram scale.
Article
Chemistry, Multidisciplinary
Allwin D. McDonald, Samantha K. Bruffy, Aadhishre T. Kasat, Andrew R. Buller
Summary: In this study, we used a substrate multiplexed screening approach to improve the substrate scope overlap in biocatalytic cascades for the synthesis of chiral 1,2-amino alcohols. By engineering the activity of enzymes, we achieved selective and efficient synthesis of enantiopure products in a one-pot cascade reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Allwin D. McDonald, Peyton M. Higgins, Andrew R. Buller
Summary: SUMS, a method for measuring enzyme activity, can be used to engineer enzymes for a wider range of substrates. This study develops principles for designing and interpreting SUMS assays, providing valuable information for improving enzyme activity, identifying variants, and determining mutational hot-spots.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Jonathan M. M. Ellis, Andrew R. R. Buller
Summary: A highly selective peptide-modifying system is computationally designed through a protein-protein interface, which sets a gold standard for studying the complex kinetic properties of designer fusion proteins.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Physical
Anna Zmich, Lydia J. Perkins, Craig Bingman, Justin F. Acheson, Andrew R. Buller
Summary: Pyridoxal phosphate (PLP)-dependent enzymes provide access to a variety of non-canonical amino acids (ncAAs), which are crucial for building complex bioactive molecules. The vinylglycineketimine (VGK) subfamily of PLP-dependent enzymes, known for its role in sulfur metabolism, includes both desirable synthases and lyases that break down ncAAs. Through substrate multiplexed screening, we identified a thermostable and highly expressive & gamma;-synthase from Caldicellulosiruptorhydrothermalis (CahyGS) that enables preparative-scale synthesis of thioether-containing ncAAs.
Article
Chemistry, Organic
Clayton M. Thompson, Allwin D. McDonald, Hanming Yang, Silvia Cavagnero, Andrew R. Buller
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)