Review
Biotechnology & Applied Microbiology
Lihong Jiang, Lei Huang, Jin Cai, Zhinan Xu, Jiazhang Lian
Summary: This article discusses the strategies for improving the expression and activity of eukaryotic P450s in yeast, followed by examples of P450s involved in biosynthetic pathway engineering.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Jose A. Amaya, David C. Lamb, Steven L. Kelly, Patrick Caffrey, Vidhi C. Murarka, Thomas L. Poulos
Summary: This study provides insights into the structural basis of substrate selectivity in the cytochrome P450 enzyme AmphL. A comparison with the closely related enzyme PimD reveals key catalytic structural features responsible for stereo- and regio-selective oxidation. The study also highlights the role of additional substrate interactions and -OH groups in correctly positioning the substrate and activating O-2. This research could contribute to the development of new macrolide antibiotics with enhanced antifungal and/or antiprotozoal efficacy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ana Silva, Maria O. Firmino, Nazua L. Costa, Ricardo O. Louro, Catarina M. Paquete
Summary: Cytochromes-c are ubiquitous heme proteins that play a key role in cellular processes such as electron transfer chains and apoptosis. The assembly of these proteins requires a maturation system called System III, which catalyzes the formation of covalent thioether bonds. This system recognizes specific amino acid sequences in the apocytochrome and facilitates heme insertion. The study found that the recognition sequence alone is not sufficient to induce maturation by System III, and the location of the sequence in the polypeptide also influences the maturation process. Additionally, System III can only catalyze the binding of one heme per polypeptide chain and cannot assemble multiheme cytochromes c, unlike bacterial maturation systems.
Article
Biochemistry & Molecular Biology
Vijay Nirusimhan, Daniel Andrew Gideon, Abhinav Parashar, Sangavi Jeyachandran, Jeyakanthan Jeyaraman, Gowthamkumar Subbaraj, Langeswaran Kulanthaivel
Summary: This study investigated the structure models of Drosophila melanogaster gut CYP450s and their differences from human counterparts, and explored the binding affinities between drugs and modeled Drosophila gut CYP450s. The results contribute to validating Drosophila as a model organism for studying intestinal drug metabolism and provide a foundation for further research on the impact of intestinal CYP450 metabolism on gut health.
CURRENT DRUG METABOLISM
(2022)
Article
Chemistry, Multidisciplinary
Peng Jiang, Hongbo Jin, Guangtao Zhang, Wenjun Zhang, Wei Liu, Yiguang Zhu, Changsheng Zhang, Liping Zhang
Summary: This study provides mechanistic understanding of the functional differences between the homologous cytochrome P450 enzymes IkaD and CftA, which catalyze multiple C-H oxidations on the same substrate with distinct regio- and chemoselectivity. The crystal structures reveal that the differences in the conformation of the F/G region in IkaD and CftA control the substrate orientation and determine their binding patterns with polar moieties. Fine-tuning the polar subpocket of IkaD can alter its regioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Tianxiang Xiao, Kai Lu
Summary: The common cutworm, Spodoptera litura, has developed resistance to commonly used insecticides. Two P450 enzymes, CYP6AE43 and CYP6AE48, play a crucial role in detoxifying pyrethroids and promoting resistance development in S. litura.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Entomology
Ralf Nauen, Chris Bass, Rene Feyereisen, John Vontas
Summary: Insect cytochrome P450 monooxygenases (P450s) play important physiological roles and are particularly involved in the detoxification of xenobiotics. Recent advances in insect genomics and functional approaches have shed light on the evolution of insect P450s, their regulation mechanisms, and the genetic alterations leading to insecticide resistance. Additionally, studies on the sensitivity of beneficial insects to insecticides have provided valuable knowledge for managing P450-mediated resistance and safeguarding their health.
ANNUAL REVIEW OF ENTOMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lisa Marie Schmitz, Felix Hageneier, Katrin Rosenthal, Tobias Busche, David Brandt, Jorn Kalinowski, Stephan Luetz
Summary: Cytochrome P450 monooxygenases play a major role in drug metabolism, and microbial P450s offer advantages in drug synthesis. Actinosynnema mirum strain has been found to have the ability to catalyze reactions on a wide range of substrates, with one substrate, ritonavir, being studied for its metabolic mechanism.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Nsikelelo Allison Malinga, Nomfundo Nzuza, Tiara Padayachee, Puleng Rosinah Syed, Rajshekhar Karpoormath, Dominik Gront, David R. Nelson, Khajamohiddin Syed
Summary: Cytochrome P450 monooxygenases in Salinispora species show high abundance and diversity, with some P450s participating in the biosynthesis of secondary metabolites, suggesting the potential for discovering novel secondary metabolites.
Article
Agronomy
Min Ye, Bidhan Nayak, Lei Xiong, Chao Xie, Yi Dong, Minsheng You, Zhiguang Yuchi, Shijun You
Summary: This article reviews the latest advances in studies related to insect P450-mediated agrochemical resistance, with focuses on the regulatory mechanisms and associated pest management strategies. Downregulation of selected P450s and the use of other strategies are promising methods to overcome resistance.
Review
Biotechnology & Applied Microbiology
Yifeng Zhang, Lin Ma, Ping Su, Luqi Huang, Wei Gao
Summary: Terpenoids, as the largest family of natural products, play significant roles in medicine, agriculture, cosmetics, and food. Traditional extraction methods have low yields, waste resources, and are not suitable for endangered species. Modern biotech approaches are promising in discovering and characterizing plant terpenoid-related P450 enzymes, and metabolic engineering strategies can be employed to increase terpenoid production.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Anup Adhikari, Sajan Shakya, Shreesti Shrestha, Dipa Aryal, Kavi Prasad Timalsina, Dipesh Dhakal, Yogan Khatri, Niranjan Parajuli
Summary: Cytochrome P450s are heme-binding monooxygenases that catalyze functionalization of various bonds, including heteroatom oxidation and C-C bond cleavage. Despite their biotechnological potential, P450s require redox partners for chemical transformations. This review focuses on the role of P450s in antibiotic biosynthesis, specifically macrolides, aminocoumarin antibiotics, NRPSs antibiotics, and RiPPs antibiotics.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Yu Shi, Shuo Sun, Yujun Zhang, Yingshi He, Minghong Du, Andrias O. OReilly, Shuwen Wu, Yihua Yang, Yidong Wu
Summary: This study investigates the functional divergence of genes in Helicoverpa armigera and related species by exchanging amino acids in the substrate recognition sites. The results show that a single amino acid substitution can alter substrate metabolism, providing insights into the process of natural selection of P450 genes and their role in insect-host plant interactions.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yu Shi, Qiong Qu, Chenyang Wang, Yingshi He, Yihua Yang, Yidong Wu
Summary: Insect CYP2 and mitochondrial clan P450 genes are found to have potential roles in chemical defense, in addition to their known involvement in biosynthesis or metabolism of endobiotics. Through in vitro experiments, it was observed that these genes in Helicoverpa armigera can catalyze the conversion of specific compounds into toxins, shedding light on the insect's chemical defense mechanisms. This study provides valuable insights into both insect chemical defense and the physiological functions of these genes in H. armigera and other insects.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Carole Belliardo, Georgios D. Koutsovoulos, Corinne Rancurel, Mathilde Clement, Justine Lipuma, Marc Bailly-Bechet, Etienne G. J. Danchin
Summary: Metagenomics has revealed the diversity of microorganisms in environmental and host-associated samples. However, current annotation pipelines are not optimized for eukaryotic contigs, leading to inaccurate annotations. By using a tailored bioinformatics pipeline, we were able to improve the quality and reliability of taxonomic annotation for eukaryotic proteins in soil metagenomes.
