CYP1 Family Research Articles

Alteration of the Catalytic Properties of the Epoxyalcohol Synthase CYP443D1 (NvEAS) of the Starlet Sea Anemone Nematostella vectensis as a Result of a Single Amino Acid Substitution.

Cytochromes of the P450 superfamily are widespread in nature; they were found in all studied aerobic organisms. Although the degree of similarity between cytochromes P450 of different families is low, all enzymes of this superfamily have similar tertiary structures. In addition, all cytochromes P450, including enzymes of the CYP74 clan, contain substrate recognition sites in their sequences, which form the catalytic center. Initially, CYP74 enzymes were discovered in plants, where they are widespread and play an important role in the lipoxygenase cascade. Later, CYP74-like enzymes of other families were identified in different taxa, including animals. Based on the results of phylogenetic studies, structures, and catalytic mechanisms, they were combined along with the CYP74 family into the CYP74 clan. One of the CYP74 clan enzymes is the epoxyalcohol synthase NvEAS (CYP443D1) of the starlet sea anemone Nematostella vectensis. A mutant form of NvEAS with a P93G substitution, that acquired additional hydroperoxide lyase activity, was obtained by site-directed mutagenesis. Before this work, only the results of site-directed mutagenesis of enzymes of the CYP74 family, but not of the CYP74 clan, were described. Moreover, in this work, the transformation of epoxyalcohol synthase into hydroperoxide lyase is described for the first time. These results confirm the previously stated assumption about the evolution of CYP74 enzymes, namely the epoxyalcohol synthase - hydroperoxide lyase - allene oxide synthase - divinyl ether synthase pathway.

Joint exploration of network pharmacology and metabolomics on the effects of traditional Chinese medicine compounds in weaned yaks.

Chinese herbal medicines are relatively inexpensive and have fewer side effects, making them an effective option for improving health and treating diseases. As a result, they have gained more attention in recent years. The weaning period is a critical stage in the life of yaks, often inducing stress in calves. Weaning stress, along with dietary changes, can lead to a decline in physical fitness and immune function, making yaks more susceptible to diarrhea and resulting in high mortality rates during this period. Therefore, our study aimed to address this issue by incorporating traditional Chinese medicine (TCM) formulas into the diet of yaks during the weaning period. Following a dialectical analysis, three TCM formulas, mainly composed of Paeonia lactiflora, Coptis chinensis, and Dandelion, were identified for their anti-inflammatory, antioxidant, and immune enhancing potentials. We explored the possible molecular mechanisms of these TCM formulas using network pharmacology analysis and investigated their effects on the physiology of yaks through metabolomics. Network pharmacology analysis revealed several key target proteins in the protein-protein interaction (PPI) network between three formulas and immune-related genes, including PIK3R1, PIK3CA, JAK2, PTK2, and PYPN11. The key target proteins in the PPI network associated with metabolism-related genes included ENPP1, CYP1A1, PTGS1, members of the CYP1 family, and EPHX2. GO analysis of co-targets revealed highly enriched pathways such as protein phosphorylation, plasma membrane, and one-carbon metabolic processes. Metabolomics revealed significant changes in the abundance of metabolites including dimethyl sulfoxide, tyrphostin A25, and thromboxane A2 in the intestines of weaned yaks supplemented with these Chinese herbal compounds. Significant changes were also observed in pathways such as vitamin A metabolism, chloroalkane, and chloroalkene degradation. Based on these findings, it can be inferred that TCM formulas improve the physical fitness of weaned yaks by enhancing antioxidant capacity, boosting immunity, and reducing intestinal inflammation. This study preliminarily elucidates the pharmacological mechanisms by which TCM formulas prevent diarrhea and improve physical fitness in weaned yaks through metabolomics and network pharmacology, paving the way for further evaluation of the effectiveness of these three formulas.

High Antennal Expression of CYP6K1 and CYP4V2 Participate in the Recognition of Alarm Pheromones by Solenopsis invicta Buren.

Insects have highly developed olfactory systems in which cytochrome P450s (CYPs) were involved as odor-degrading enzymes throughout the olfactory recognition of odor compounds by insects to avoid continuous stimulation of signaling molecules and thus damage to the olfactory nervous. To understand whether the highly expressed CYPs in the antennae play an olfactory function in Solenopsis invicta worker, in this study, we find six highly expressed antennal CYPs from the transcriptome of S. invicta. Multiple sequence alignment and phylogenetic analysis divided them into two families: the CYP3 family (SinvCYP6K1, SinvCYP6K1-1) and the CYP4 family (SinvCYP4C1, SinvCYP4C1-1, SinvCYP4C1-2, SinvCYP4V2). The expression patterns of these six CYPs were analyzed by RT-qPCR, which revealed that SinvCYP6K1 and SinvCYP4V2 were only highly expressed in the antennae of adult workers. The expression of SinvCYP6K1 and SinvCYP4V2 in workers was markedly diminished after feeding with dsRNA. The electroantennography (EAG) assay demonstrated that the silencing of either SinvCYP6K1 or SinvCYP4V2 resulted in a notable reduction in the EAG response of workers to 2-ethyl-3,6(5)-dimethylpyrazine (EDMP). Furthermore, the trajectory behavior assay showed that the worker's range and speed of movement in response to EDMP significant decreased after the silencing of SinvCYP6K1 and SinvCYP4V2. The findings indicated that both SinvCYP6K1 and SinvCYP4V2 were implicated in the recognition of EDMP by S. invicta.

DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.

Background and Aims: Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients' tumors but not in other liver cancers. Since previous studies of J-PKAc were performed with adolescent patients, we asked if young children may express J-PKAc and if there are consequences of such expression. Methods: The biobank of the pediatric HBL/HCN-NOS specimens was examined by QRT-PCR, Western blots, RNA-Seq, and immunostaining with fusion-specific antibodies. Results: J-PKAc is expressed in 70% of the HBL/HCN-NOS patients. RNA-Seq analysis revealed that HBL tumors that do not have cells expressing J-PKAc show elevated expression of the membrane attack complex (MAC), which eliminates cells expressing J-PKAc. The fusion-positive HBL/HCN-NOS samples have several signaling pathways that are different from fusion-negative HBLs. Upregulated pathways included genes involved in the G1 to S transition and in liver cancer. Downregulated pathways included over 60 tumor suppressors, the CYP family, and the SLC family. The repression of these genes involves J-PKAc-β-catenin-TCF4-mediated elevation of the HDAC1-Sp5 pathway. The identified upregulated and downregulated pathways are direct targets of the fusion kinase. The J-PKAc kinase is also detected in livers of 1-year-old children with biliary atresia (BA). Conclusions: J-PKAc is expressed in both HBL tumor and BA liver samples, contributing to the development of HBL and creating a transcriptome profiling consistent with the potential development of liver cancer in young patients.

Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections.

Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis. Furthermore, most studies investigating the role of Cyps in viral hepatitis did not investigate the potential therapeutic effects of their inhibition in already-established infections but have rather been performed in the context of neo-infections. Here, we investigated the effects of genetically silencing Cyps on persistent HCV and HBV infections. We confirm antiviral effects of CypA and CypD knock down and demonstrate novel roles for CypG and CypH in HCV replication. We show, furthermore, that CypA silencing has a modest but reproducible impact on persistent HBV infections in cultured human hepatocytes.

Plasticity in Gene Expression Patterns and CYPSF Gene Possibly Involved in the Etofenprox-Resistant Population of White-Backed Planthopper, Sogatella furcifera.

The white-backed planthopper (WBPH) poses a significant threat to rice crops globally. A bioassay was conducted on three WBPH populations collected from Korean rice fields to assess the effectiveness of five insecticides, including etofenprox and fenobucarb. The results showed a mortality rate of over 97% at the recommended concentration for carbamate and organophosphate insecticides. However, etofenprox exhibited a mortality rate of less than 40% in all tested populations with the Jindo population showing the highest resistance. No mutations were identified in the voltage-sensitive sodium channel, the target site of etofenprox, suggesting an alternative resistance mechanism. To explore this, RNA-seq analysis was performed on the Jindo population to identify genes potentially associated with etofenprox resistance. Gene expression was assessed after treatment with two sublethal doses of etofenprox using the Jindo population. The analysis revealed that the CYPSF gene, part of the CYP6 family, was consistently overexpressed in both treated and untreated samples. This observation aligns with the bioassay results, where mortality increased significantly after treatment with the cytochrome P450 inhibitor PBO, indicating that CYPSF may play a key role in etofenprox resistance. Additionally, distinct gene expression patterns at different etofenprox concentrations suggest that metabolic resistance mechanisms may be involved.

Identification and characterization of the cytochrome p450 complement in <i>Streptomyces cavourensis</i> YBQ59

Cytochrome P450 enzymes (CYPs) are regarded as some of the most versatile biocatalysts. They are attractive candidates for natural product development because of their ability to selectively oxidize a broad range of substrates. Streptomyces spp. are not only producers of biologically active secondary metabolites but also a rich source of P450 enzymes. However, only a limited number of studies have explored the function and potential of P450 enzymes encoded in the Streptomyces genomes. In this study, the endophytic Streptomyces cavourensis YBQ59 isolated from Cinnamomum cassia J. Presl was sequenced using the Illumina sequencing platform to identify its P450 enzymes. The genome of YBQ59 was approximately 8,126,002 bp in size, with a G + C content of 72.1% and contained 7,020 genes. Genome annotation identified 21 CYP genes, distributed across 10 CYP families and 17 subfamilies. The possible role of these P450 enzymes in the synthesis of secondary metabolites was discussed. Since CYPs often require electron transport proteins to function, we analyzed the physical map of the genes encoding ferredoxins and ferredoxin reductases found in the genome of S. cavourensis YBQ59. Additionally, a phylogenetic tree was constructed to compare the P450 enzyme system from S. cavourensis YBQ59 with those of closely related and well-studied Streptomyces species, including Streptomyces sp. CFMR7, S. fulvissimus DSM 40593, S. griseus IFO 13350, and S. globisporus 1912. These results provide a basis for exploiting potential P450 enzymes from S. cavourensis YBQ59 for agricultural and medicinal applications.

Genomic, transcriptomic, and metabolomic analyses reveal convergent evolution of oxime biosynthesis in Darwin's orchid.

Angraecum sesquipedale, also known as Darwin's orchid, possesses an exceptionally long nectar spur. Charles Darwin predicted the orchid to be pollinated by a hawkmoth with a correspondingly long proboscis, later identified as Xanthopan praedicta. In this plant-pollinator interaction, the A. sesquipedale flower emits a complex blend of scent compounds dominated by diurnally regulated oximes (R1R2C=N-OH) to attract crepuscular and nocturnal pollinators. The molecular mechanism of oxime biosynthesis remains unclear in orchids. Here, we present the chromosome-level genome of A. sesquipedale. The haploid genome size is 2.10 Gb and represents 19 pseudochromosomes. Cytochrome P450 encoding genes of the CYP79 family known to be involved in oxime biosynthesis in seed plants are not present in the A. sesquipedale genome nor in the genomes of other members of the orchid family. Metabolomic analysis of the A. sesquipedale flower revealed a substantial release of oximes at dusk during the blooming stage. By integrating metabolomic and transcriptomic correlation approaches, flavin-containing monooxygenases (FMOs) encoded by six tandem-repeat genes in the A. sesquipedale genome are identified as catalyzing the formation of oximes present. Further in vitro and in vivo assays confirm the function of FMOs in the oxime biosynthesis. We designate these FMOs as Orchid Oxime Synthases 1-6. The evolutionary aspects related to the CYP79 gene losses and neofunctionalization of FMO-catalyzed biosynthesis of oximes in Darwin's orchid provide new insights into the convergent evolution of biosynthetic pathways.

Knockdown of CYP6SZ3 and CYP6AEL1 genes increases the susceptibility of Lasioderma serricorne to ethyl formate and benzothiazole.

Insect cytochrome P450 monooxygenases (CYPs) play crucial roles in the metabolic detoxification of insecticides. Ethyl formate and benzothiazole have recently regained popularity as fumigants due to rising resistance to phosphine in the stored-product pests. However, the mechanisms underlying tolerance to these two fumigants in Lasioderma serricorne, a major global insect pest of stored products, remain poorly understood. In this study, two CYP genes, named CYP6SZ3 and CYP6AEL1, were identified from L. serricorne, belonging to the CYP6 family and containing five conserved domains characteristic of CYP proteins. Spatiotemporal expression analysis revealed that both genes were predominantly expressed in the larval stage and showed the highest expression in the foregut. Upon exposure to ethyl formate and benzothiazole, both genes were upregulated, with significantly increased transcription levels following treatment. RNA interference-mediated silencing of CYP6SZ3 and CYP6AEL1 led to increased susceptibility and significantly higher mortality of L. serricorne when exposed to these fumigants. Homology modeling and molecular docking analyses showed stable binding of these fumigants to CYP6SZ3 and CYP6AEL1 proteins, with binding free energies from -26.88 to -94.68 kcal mol-1. These findings suggest that the induction of CYP6SZ3 and CYP6AEL1 is likely involved in the detoxification of ethyl formate and benzothiazole in L. serricorne.

Assessing the stereoselective bioactivity and biotoxicity of penthiopyrad in soil environment for efficacy improvement and hazard reduction

Penthiopyrad, a chiral pesticide, has been widely used in agricultural production. However, systematic evaluation of stereoselective bioactivity and biotoxicity of penthiopyrad in soil environment is insufficient. In this study, the stereoselective bioactivity of penthiopyrad against three soil-borne disease pathogens and its stereoselective biotoxicity to soil non-target organisms were investigated. The present results showed that the bioactivities of S-penthiopyrad were 546, 76 and 1.1-fold higher than those of R-penthiopyrad due to their different interaction modes with SDH in different target pathogens. S-penthiopyrad was more persistent in the soil environment and had stronger bioaccumulation than R-penthiopyrad. The accumulation of penthiopyrad in earthworms induced the response of detoxification system, resulting in the significant increases in the activity of detoxifying enzymes, such as GST, CarE, and CYP450. Additionally, both S-penthiopyrad and R-penthiopyrad induced cell apoptosis, intestinal damage and differentially expressed genes in earthworms, especially S-penthiopyrad. Furthermore, S-penthiopyrad has stronger binding capacity with COL6A and ACE proteins, while R-penthiopyrad has stronger binding capacity with CYP450 family proteins, which may be the main reason for the differences in biotoxicity between PEN enantiomers. Considering the differences in bioactivity and biotoxicity of penthiopyrad enantiomers, as well as the modes of action of pesticides on target and non-target organisms, S-penthiopyrad has greater potential for future development.

Unveiling dynamic hepatocyte plasticity in HepaRG cells with a dual CYP reporter system.

Primary hepatocytes are widely utilized for investigating drug efficacy and toxicity, yet variations between batches and limited proliferation capacity present significant challenges. HepaRG cells are versatile cells, capable of maintaining an undifferentiated state and differentiating through dimethyl sulfoxide treatment, allowing for molecular analysis of hepatocyte plasticity. To elucidate the underlying molecular mechanisms of HepaRG cell plasticity, we used CYP3A4G/7R HepaRG cells engineered to express DsRed under the control of the fetus-specific CYP3A7 gene and EGFP under the adult-specific CYP3A4 gene promoter. In time-lapse imaging of CYP3A4G/7R HepaRG cells, we observed CYP3A7-DsRed expression transitioning from negative to positive during proliferation period and CYP3A4-GFP expression activating during differentiation. The de-differentiation potency of differentiated CYP3A4G/7R HepaRG cells was assessed using inhibitors and cytokines. It was found that Y-27632 (Y), A-83-01 (A), and CHIR99021 (C) (collectively referred to as YAC), which are known to promote liver regeneration in mice, did not induce CYP3A7-DsRed expression. Instead, these inhibitors increased CYP3A4-GFP expressing population. Furthermore, CHIR99021 alone increased CYP3A4-GFP-positive cells, while Wnt3a treatment increased CYP3A7-DsRed-positive cells, suggesting that Wnt signaling plays distinct roles in HepaRG cells. It was apparent that de-differentiated cells had increased CYP3A4 activity after a second round of differentiation, compared to differentiated cells after the first round. Transcriptomic analysis of HepaRG cells revealed distinct profiles between proliferative, differentiated, and de-differentiated states, highlighting their robust plasticity. Notably, hepatoblastic cells de-differentiated by YAC or C displayed transcriptome patterns similar to undifferentiated cells, whereas CYP3A7-DsRed and CYP3A4-GFP exhibited expression patterns different from those of undifferentiated cells. These findings underscore the dynamic nature of HepaRG cells while cautioning against solely relying on CYP3 family gene expression as a marker of differentiation.

Comprehensive Review on Plant Cytochrome P450 Evolution: Copy Number, Diversity, and Motif Analysis From Chlorophyta to Dicotyledoneae.

Cytochrome P450 enzymes (CYPs) are widely distributed among various plant groups and constitute approximately 1% of the total number of protein-coding genes. Extensive studies suggest that CYPs are involved in nearly all molecular processes that occur in plants. Over the past two decades, the identification of CYP genes has expanded rapidly, with more than 40,000 CYP genes and 819 CYP families being discovered. Copy number variation is a significant evolutionary characteristic of gene families, yet a systematic characterization of the copy evolution patterns in plant CYP gene families has been lacking, resulting in confusion and challenges in understanding CYP functions. To address these concerns, this review provides comprehensive statistics and analyses of the copy number and diversity of almost all plant CYP gene families, focusing on CYP evolution from Chlorophyta to Dicotyledoneae. Additionally, we examined the subfamily characteristics of certain CYP families with restricted copy changes and identified several CYP subfamilies that play pivotal roles in this event. Furthermore, we analyzed the structural conservation of CYPs across different taxa and compiled a comprehensive database to support plant CYP studies. Our analysis revealed differences in the six core conserved motifs of plant CYP proteins among various clans and plant taxa, while demonstrating similar conservation patterns for the ERR (glutamic acid-arginine-arginine) triad motifs. These findings will significantly facilitate the understanding of plant CYP gene evolution and metabolic diversity and serve as a valuable reference for researchers studying CYP enzymes.

Sequence diversity in the monooxygenases involved in oxime production in plant defense and signaling: a conservative revision in the nomenclature of the highly complex CYP79 family.

Cytochrome P450 monooxygenases of the CYP79 family catalyze conversion of specific amino acids into oximes feeding into a variety of metabolic plant pathways. Here we present an extensive phylogenetic tree of the CYP79 family built on carefully curated sequences collected across the entire plant kingdom. Based on a monophyletic origin of the P450s, a set of evolutionarily distinct branches was identified. Founded on the functionally characterized CYP79 sequences, sequence features of the individual substrate recognition sites (SRSs) were analyzed. Co-evolving amino acid residues were identified using co-evolutionary sequence analysis. SRS4 possesses a specific sequence pattern when tyrosine is a substrate. Except for the CYP79Cs and CYP79Fs, substrate preferences toward specific amino acids could not be assigned to specific subfamilies. The highly diversified CYP79 tree, reflecting recurrent independent evolution of CYP79s, may relate to the different roles of oximes in different plant species. The sequence differences across individual CYP79 subfamilies may facilitate the in vivo orchestration of channeled metabolic pathways based on altered surface charge domains of the CYP79 protein. Alternatively, they may serve to optimize dynamic interactions with oxime metabolizing enzymes to enable optimal ecological interactions. The outlined detailed curation of the CYP79 sequences used for building the phylogenetic tree made it appropriate to make a conservative phylogenetic tree-based revision of the naming of the sequences within this highly complex cytochrome P450 family. The same approach may be used in other complex P450 subfamilies. The detailed phylogeny of the CYP79 family will enable further exploration of the evolution of function in these enzymes.

The Synergistic and Opposing Roles of ω-Fatty Acid Hydroxylase (CYP4A11) and ω-1 Fatty Acid Hydroxylase (CYP2E1) in Chronic Liver Disease

Cytochrome P450 fatty acid hydroxylase consists of members of the CYP4 family that ω-hydroxylate fatty acids and the CYP2E1 that ω-1 hydroxylates fatty acids. Although ω and ω-1 hydroxylation of fatty acids have been thought to play a minor role in fatty acid metabolism (less than 20%), it plays a vital role in excess liver fatty acids overload seen in fasting, diabetes, metabolic disorder, and over-consumption of alcohol and high-fat diet. This pathway provides anabolic metabolites for gluconeogenesis, succinate, and acetate for lipogenesis. The CYP4A and CYP2E1 genes are activated in fasting and several metabolic disorders, suggesting a synergistic role in preventing fatty acid-induced lipotoxicity with the consequence of increased liver cholesterol and lipogenesis leading to increased Lipid Droplet (LD) deposition. During the progression of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), activation of Phospholipase A2 (PLA2) releases arachidonic acid that CYP4A11 and CYP2E1 P450s metabolize to produce 20-hydroxyeicosatetraenoic acid (20-HETE) and 19-HETE, respectively. These metabolites have opposing roles in the progression of MASLD and chronic liver disease (CLD). This report discusses the synergistic role of the CYP4A and CYP2E1 P450s in the metabolism of saturated and unsaturated fatty acids and their opposite physiological role in the metabolism of Arachidonic Acid (AA). We finally discuss the role of ethanol in disrupting the synergistic and opposing roles of the CYP4A and CYP2E1 genes in MASLD and CLD.

Genome-wide screen and multi-omics analysis reveal OGT1 participate in the biosynthesis of safflower flavonoid glycosides.

Safflower, an economic crop, is renowned for its flowers, which are widely used in medicines for treating cardiovascular and cerebrovascular diseases and in dyes for food and industry. The utility of safflower depends on its flavonoid glycosides. Therefore, the biosynthesis of safflower flavonoid glycosides has been a focus of attention, but the present mechanisms remain poorly understood. This study aims to identify functional genes associated with flavonoid glycoside biosynthesis in safflower through a comprehensive approach that integrates whole-genome screen and multi-omics correlation studies. CYP and UGT are two crucial genes families involved in flavonoid glycoside biosynthesis. We have screened 264 CYP genes and 140 UGT genes in the genome of safflower and conducted analyzes including phylogenetic relationships, conserved motifs, gene structures, cis-acting elements, and chromosome mapping, which provided extensive and comprehensive data on the CYP and UGT gene families. Integration of phenotype and metabolic data from safflower different tissues helped narrow down the screening by confirming that HSYA is synthesized only in flowers. Based on the gene expression patterns and phylogenetic analysis, CtOGT1 was ultimately identified, which could catalyze the generation of glycosides using various flavonoid substrates and exhibited strong substrate affinity. Moreover, molecular docking studies elucidated CtOGT1's highly active intrinsic mechanism. In conclusion, this study effectively identified genes responsible for flavonoid glycoside biosynthesis in safflower through the integration of whole-genome screen and multi-omics analysis, established a comprehensive foundation of data, methodology, and experimental evidence for further elucidating the pathways of safflower flavonoid glycoside biosynthesis.

Drug Metabolizing Enzymes: An Exclusive Guide into Latest Research in Pharmaco-genetic Dynamics in Arab Countries.

Drug metabolizing enzymes play a crucial role in the pharmacokinetics and pharmacodynamics of therapeutic drugs, influencing their efficacy and safety. This review explores the impact of genetic polymorphisms in drug-metabolizing genes on drug response within Arab populations. We examine the genetic diversity specific to Arab countries, focusing on the variations in key drug-metabolizing enzymes such as CYP450, GST, and UGT families. The review highlights recent research on polymorphisms in these genes and their implications for drug metabolism, including variations in allele frequencies and their effects on therapeutic outcomes. Additionally, the paper discusses how these genetic variations contribute to the variability in drug response and adverse drug reactions among individuals in Arab populations. By synthesizing current findings, this review aims to provide a comprehensive understanding of the pharmacogenetic landscape in Arab countries and offer insights into personalized medicine approaches tailored to genetic profiles. The findings underscore the importance of incorporating pharmacogenetic data into clinical practice to enhance drug efficacy and minimize adverse effects, ultimately paving the way for more effective and individualized treatment strategies in the region.

Biochemical and molecular characterization of pyrifluquinazon resistance in Bemisia tabaci Asia I

One of the most devastating polyphagous pests in the world, Bemisia tabaci (Gennadius), causes significant damage to a variety of crops and has demonstrated the ability to develop resistance to different classes of insecticides rapidly. A novel pyridine azomethine derivative pyrifluquinazon exhibits exceptional insecticidal toxicity against B. tabaci by interrupting the function of chordotonal receptor neurons. Formulating resistance management strategies is crucial to ensure the long-term use of this insecticide for whitefly control; however, the characteristics and possible mechanisms of pyrifluquinazon resistance in B. tabaci remain unclear. By employing pyrifluquinazon selection for 22 successive generations, the pyrifluquinazon-resistant strain (PQZ-R) was generated from a laboratory-susceptible population of B. tabaci Asia I (Lab-WB) and exhibited 39.65-fold resistance to pyrifluquinazon. When the realized heritability (h2) of B. tabaci to pyrifluquinazon was assumed to be the laboratory-estimated value (h2 = 0.181) and the mortality was 70–90%, only 12.3–22.6 generations were expected to be required to obtain a 10-fold increase in pyrifluquinazon resistance. While there was no significant cross-resistance to cyantraniliprole, dinotefuran, flonicamid, flupyradifurone, pymetrozine, sulfoxaflor, or thiamethoxam, the PQZ-R strain displayed slight cross-resistance to afidopyropen (3.14-fold). Synergism tests indicated that piperonyl butoxide (PBO) inhibits (4.36-fold) pyrifluquinazon resistance in the PQZ-R strain. This impact may be attributed to enhanced detoxification (elevated 3.91-fold) mediated by cytochrome P450 monooxygenase (P450). Compared to Lab-WB, the PQZ-R strain exhibited no significant overexpression of the 13 published detoxification-related P450 genes from CYP303, CYP4, and CYP6 families in B. tabaci. The combined knowledge gained from this study will enable further investigations into the function of qualitative and quantitative variations in P450-encoded genes, leading to innovative approaches for efficiently managing B. tabaci.

Identification and expression dynamics of CYPome across different developmental stages of Maconellicoccus hirsutus (Green)

Maconellicoccus hirsutus is a highly polyphagous insect pest, posing a substantial threat to various crop sp., especially in the tropical and sub-tropical regions of the world. While extensive physiological and biological studies have been conducted on this pest, the lack of genetic information has hindered our understanding of the molecular mechanisms underlying its growth, development, and xenobiotic metabolism. The Cytochrome P450 gene, a member of the CYP gene superfamily ubiquitous in living organisms is associated with growth, development, and the metabolism of both endogenous and exogenous substances, contributing to the insect's adaptability in diverse environments. To elucidate the specific role of the CYP450 gene family in M. hirsutus which has remained largely unexplored, a de novo transcriptome assembly of the pink mealybug was constructed. A total of 120 proteins were annotated as CYP450 genes through homology search of the predicted protein sequences across different databases. Phylogenetic studies resulted in categorizing 120 CYP450 genes into four CYP clans. A total of 22 CYP450 families and 30 subfamilies were categorized, with CYP6 forming the dominant family. The study also revealed five genes (Halloween genes) associated with the insect hormone biosynthesis pathway. Further, the expression of ten selected CYP450 genes was studied using qRT-PCR across crawler, nymph, and adult stages, and identified genes that were expressed at specific stages of the insects. Thus, the findings of this study reveal the expression dynamics and possible function of the CYP450 gene family in the growth, development, and adaptive strategies of M. hirsutus which can be further functionally validated.

Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review.

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.

Changes of Active Substances in Ganoderma lucidum during Different Growth Periods and Analysis of Their Molecular Mechanism.

Ganoderma lucidum, renowned as an essential edible and medicinal mushroom in China, remains shrouded in limited understanding concerning the intrinsic mechanisms governing the accumulation of active components and potential protein expression across its diverse developmental stages. Accordingly, this study employed a meticulous integration of metabolomics and proteomics techniques to scrutinize the dynamic alterations in metabolite accumulation and protein expression in G. lucidum throughout its growth phases. The metabolomics analysis unveiled elevated levels of triterpenoids, steroids, and polyphenolic compounds during the budding stage (BS) of mushroom growth, with prominent compounds including Diplazium and Ganoderenic acids E, H, and I, alongside key steroids such as cholesterol and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol. Additionally, nutrients such as polysaccharides, flavonoids, and purines exhibited heightened presence during the maturation stage (FS) of ascospores. Proteomic scrutiny demonstrated the modulation of triterpenoid synthesis by the CYP450, HMGR, HMGS, and ERG protein families, all exhibiting a decline as G. lucidum progressed, except for the ARE family, which displayed an upward trajectory. Therefore, BS is recommended as the best harvesting period for G. lucidum. This investigation contributes novel insights into the holistic exploitation of G. lucidum.