共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Shuhan Yu Qiguo Sun Jiaxuan Wu Pengcheng Zhao Yanmei Sun Zhenfei Guo 《International journal of molecular sciences》2021,22(17)
Short-chain dehydrogenase/reductase (SDR) belongs to the NAD(P)(H)-dependent oxidoreductase superfamily. Limited investigations reveal that SDRs participate in diverse metabolisms. A genome-wide identification of the SDR gene family in M. truncatula was conducted. A total of 213 MtSDR genes were identified, and they were distributed on all chromosomes unevenly. MtSDR proteins were categorized into seven subgroups based on phylogenetic analysis and three types including ‘classic’, ‘extended’, and ‘atypical’, depending on the cofactor-binding site and active site. Analysis of the data from M. truncatula Gene Expression Atlas (MtGEA) showed that above half of MtSDRs were expressed in at least one organ, and lots of MtSDRs had a preference in a tissue-specific expression. The cis-acting element responsive to plant hormones (salicylic acid, ABA, auxin, MeJA, and gibberellin) and stresses were found in the promoter of some MtSDRs. Many genes of MtSDR7C, MtSDR65C, MtSDR110C, MtSDR114C, and MtSDR108E families were responsive to drought, salt, and cold. The study provides useful information for further investigation on biological functions of MtSDRs, especially in abiotic stress adaptation, in the future. 相似文献
3.
Yuanyuan Zhao Junchao Zhang Zhanmin Sun Yixiong Tang Yanmin Wu 《International journal of molecular sciences》2021,22(14)
Polycomb group (PcG) proteins, which are important epigenetic regulators, play essential roles in the regulatory networks involved in plant growth, development, and environmental stress responses. Currently, as far as we know, no comprehensive and systematic study has been carried out on the PcG family in Medicago truncatula. In the present study, we identified 64 PcG genes with distinct gene structures from the M. truncatula genome. All of the PcG genes were distributed unevenly over eight chromosomes, of which 26 genes underwent gene duplication. The prediction of protein interaction network indicated that 34 M. truncatula PcG proteins exhibited protein–protein interactions, and MtMSI1;4 and MtVRN2 had the largest number of protein–protein interactions. Based on phylogenetic analysis, we divided 375 PcG proteins from 27 species into three groups and nine subgroups. Group I and Group III were composed of five components from the PRC1 complex, and Group II was composed of four components from the PRC2 complex. Additionally, we found that seven PcG proteins in M. truncatula were closely related to the corresponding proteins of Cicer arietinum. Syntenic analysis revealed that PcG proteins had evolved more conservatively in dicots than in monocots. M. truncatula had the most collinearity relationships with Glycine max (36 genes), while collinearity with three monocots was rare (eight genes). The analysis of various types of expression data suggested that PcG genes were involved in the regulation and response process of M. truncatula in multiple developmental stages, in different tissues, and for various environmental stimuli. Meanwhile, many differentially expressed genes (DEGs) were identified in the RNA-seq data, which had potential research value in further studies on gene function verification. These findings provide novel and detailed information on the M. truncatula PcG family, and in the future it would be helpful to carry out related research on the PcG family in other legumes. 相似文献
4.
SangKil Lee DeviB. Basnet JaySungJoong Hong WonSeok Jung ChaYong Choi HeiChan Lee JaeKyung Sohng KeunGarp Ryu DaeJoong Kim JongSeog Ahn BeomSeok Kim HyunCheol Oh DavidH. Sherman Yeo JoonYoon 《Advanced Synthesis \u0026amp; Catalysis》2005,347(10):1369-1378
The substrate flexibilities of several cytochrome P450 monooxygenases involved in macrolide biosynthesis were investigated to test their potential for the generation of novel macrolides. PikC hydroxylase in the pikromycin producer Streptomyces venezuelae accepted oleandomycin as an alternative substrate and introduced a hydroxy group at the C‐4 position, which is different from the intrinsic C‐12 hydroxylation position in the natural substrate. This is the first report of C‐4 hydroxylation activity of cytochrome P450 monooxygenase involved in the biosynthesis of 14‐membered macrolides. EryF hydroxylase from the erythromycin biosynthetic pathway of Saccharopolyspora erythraea and OleP oxidase from the oleandomycin biosynthetic pathway of Streptomyces antibioticus also showed a certain degree of plasticity towards alternative substrates. In particular, EryF and OleP were found to oxidize a 12‐membered macrolactone as an alternative substrate. These results demonstrate the potential usefulness of these enzymes to diversify macrolactones by post‐PKS oxidations. 相似文献
5.
Jiawei Liu Hongmin Hu Huimin Shen Qingyin Tian Wenjie Ding Xiulian Yang Lianggui Wang Yuanzheng Yue 《International journal of molecular sciences》2022,23(20)
Osmanthus fragrans flowers have long been used as raw materials in food, tea, beverage, and perfume industries due to their attractive and strong fragrance. The P450 superfamily proteins have been reported to widely participate in the synthesis of plant floral volatile organic compounds (VOCs). To investigate the potential functions of P450 superfamily proteins in the fragrance synthesis of O. fragrans, we investigated the P450 superfamily genome wide. A total of 276 P450 genes were identified belonging to 40 families. The RNA-seq data suggested that many OfCYP genes were preferentially expressed in the flower or other organs, and some were also induced by multiple abiotic stresses. The expression patterns of seven flower-preferentially expressed OfCYPs during the five different flower aroma content stages were further explored using quantitative real-time PCR, showing that the CYP94C subfamily member OfCYP142 had the highest positive correlation with linalool synthesis gene OfTPS2. The transient expression of OfCYP142 in O. fragrans petals suggested that OfCYP142 can increase the content of linalool, an important VOC of the O. fragrans floral aroma, and a similar result was also obtained in flowers of OfCYP142 transgenic tobacco. Combined with RNA-seq data of the transiently transformed O. fragrans petals, we found that the biosynthesis pathway of secondary metabolites was significantly enriched, and many 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway genes were also upregulated. This evidence indicated that the OfCYP proteins may play critical roles in the flower development and abiotic response of O. fragrans, and that OfCYP142 can participate in linalool synthesis. This study provides valuable information about the functions of P450 genes and a valuable guide for studying further functions of OfCYPs in promoting fragrance biosynthesis of ornamental plants. 相似文献
6.
Dr. Chengchang Zhang Dr. Meiling Lu Dr. Lin Lin Prof. Dr. Zhangjian Huang Prof. Dr. Rongguang Zhang Dr. Xuri Wu Prof. Dr. Yijun Chen 《Chembiochem : a European journal of chemical biology》2020,21(16):2297-2305
Like a vast number of enzymes in nature, bacterial cytochrome P450 monooxygenases require an activated form of flavin as a cofactor for catalytic activity. Riboflavin is the precursor of FAD and FMN that serves as indispensable cofactor for flavoenzymes. In contrast to previous notions, herein we describe the identification of an electron-transfer process that is directly mediated by riboflavin for N-dealkylation by bacterial P450 monooxygenases. The electron relay from NADPH to riboflavin and then via activated oxygen to heme was proposed based on a combination of X-ray crystallography, molecular modeling and molecular dynamics simulation, site-directed mutagenesis and biochemical analysis of representative bacterial P450 monooxygenases. This study provides new insights into the electron transfer mechanism in bacterial P450 enzyme catalysis and likely in yeasts, fungi, plants and mammals. 相似文献
7.
Didem Yıldırım Cem Ozic Dr. Yunus Ensari 《Chembiochem : a European journal of chemical biology》2023,24(12):e202300065
Oxyfunctionalization of non-activated carbon bonds by P450 monooxygenases has drawn great industrial attraction. Self-sufficient P450s containing catalytic heme and reductase domains in a single polypeptide chain offer many advantages since they do not require external electron transfer partners. Here, we report the first P450 enzyme identified and expressed from Azorhizobium caulinodans. Firstly, expression conditions of P450 AZC1 were optimized for enhanced expression in E.coli. The highest P450 content was obtained in E.coli Rosetta DE3 plysS when it was incubated in TB media supplemented with 0.75 mM IPTG, 0.5 mM ALA, and 0.75 mM FeCl3 at 25 °C for 24 hours. Subsequently, the purified enzyme showed a broad substrate spectrum including fatty acids, linear and cyclic alkanes, aromatics, and pharmaceuticals. Finally, P450 AZC1 showed optimal activity at pH 6.0 and 40 °C and a broad pH and temperature profile, making it a promising candidate for industrial applications. 相似文献
8.
Cytochrome P450 reductase (CYPOR) provides electrons to all human microsomal cytochrome P450s (cyt P450s). The length and sequence of the “140s” FMN binding loop of CYPOR has been shown to be a key determinant of its redox potential and activity with cyt P450s. Shortening the “140s loop” by deleting glycine-141(ΔGly141) and by engineering a second mutant that mimics flavo-cytochrome P450 BM3 (ΔGly141/Glu142Asn) resulted in mutants that formed an unstable anionic semiquinone. In an attempt to understand the molecular basis of the inability of these mutants to support activity with cyt P450, we expressed, purified, and determined their ability to reduce ferric P450. Our results showed that the ΔGly141 mutant with a very mobile loop only reduced ~7% of cyt P450 with a rate similar to that of the wild type. On the other hand, the more stable loop in the ΔGly141/Glu142Asn mutant allowed for ~55% of the cyt P450 to be reduced ~60% faster than the wild type. Our results reveal that the poor activity of the ΔGly141 mutant is primarily accounted for by its markedly diminished ability to reduce ferric cyt P450. In contrast, the poor activity of the ΔGly141/Glu142Asn mutant is presumably a consequence of the altered structure and mobility of the “140s loop”. 相似文献
9.
10.
11.
Lingzhi Xie Ke Chen Haibo Cui Dr. Nanwei Wan Dr. Baodong Cui Dr. Wenyong Han Prof. Dr. Yongzheng Chen 《Chembiochem : a European journal of chemical biology》2020,21(13):1820-1825
A self-sufficient cytochrome P450 monooxygenase from Deinococcus apachensis (P450DA) was identified and successfully overexpressed in Escherichia coli BL21(DE3). P450DA would be a member of the CYP102D subfamily and assigned as CYP102D2 according to the phylogenetic tree and sequence alignment. Purification and characterization of the recombinant P450DA indicated both NADH and NADPH could be used by P450DA as a reducing cofactor. The recombinant E. coli (P450DA) strain was functionally active, showing excellent enantioselectivity for benzylic hydroxylation of methyl 2-phenylacetate. Further substrate scope studies revealed that P450DA is able to catalyze benzylic hydroxylation of a variety of compounds, affording the corresponding chiral benzylic alcohols in 86–99 % ee and 130–1020 total turnover numbers. 相似文献
12.
13.
Mingzhe Zhao Jingsong Ma Mo Li Yingtian Zhang Bixuan Jiang Xianglong Zhao Cong Huai Lu Shen Na Zhang Lin He Shengying Qin 《International journal of molecular sciences》2021,22(23)
Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy. 相似文献
14.
15.
16.
Nomfundo Nzuza Tiara Padayachee Puleng Rosinah Syed Justyna Dorota Kry Wanping Chen Dominik Gront David R. Nelson Khajamohiddin Syed 《International journal of molecular sciences》2021,22(11)
Cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolate proteins, are well-known players in the generation of chemicals valuable to humans and as a drug target against pathogens. Understanding the evolution of P450s in a bacterial population is gaining momentum. In this study, we report comprehensive analysis of P450s in the ancient group of the bacterial class Alphaproteobacteria. Genome data mining and annotation of P450s in 599 alphaproteobacterial species belonging to 164 genera revealed the presence of P450s in only 241 species belonging to 82 genera that are grouped into 143 P450 families and 214 P450 subfamilies, including 77 new P450 families. Alphaproteobacterial species have the highest average number of P450s compared to Firmicutes species and cyanobacterial species. The lowest percentage of alphaproteobacterial species P450s (2.4%) was found to be part of secondary metabolite biosynthetic gene clusters (BGCs), compared other bacterial species, indicating that during evolution large numbers of P450s became part of BGCs in other bacterial species. Our study identified that some of the P450 families found in alphaproteobacterial species were passed to other bacterial species. This is the first study to report on the identification of CYP125 P450, cholesterol and cholest-4-en-3-one hydroxylase in alphaproteobacterial species (Phenylobacterium zucineum) and to predict cholesterol side-chain oxidation capability (based on homolog proteins) by P. zucineum. 相似文献
17.
Wenting Dai Bin Zhu Marcel van Tuinen Tao Zhu Dongliang Shang Pedro Almeida Pei Liang Hidayat Ullah Liping Ban 《International journal of molecular sciences》2022,23(20)
Pesticide resistance in insects is an example of adaptive evolution occurring in pest species and is driven by the artificial introduction of pesticides. The diamondback moth (DBM), Plutella xylostella (Lepidoptera: Plutellidae), has evolved resistance to various insecticides. Understanding the genetic changes underpinning the resistance to pesticides is necessary for the implementation of pest control measures. We sequenced the genome of six resistant and six susceptible DBM individuals separately and inferred the genomic regions of greatest divergence between strains using FST and θπ. Among several genomic regions potentially related to insecticide resistance, CYP6B6-like was observed with significant divergence between the resistant and susceptible strains, with a missense mutation located near the substrate recognition site (SRS) and four SNPs in the promoter. To characterize the relative effects of directional selection via insecticide tolerance (‘strain’) as compared to acute exposure to insecticide (‘treatment’), four pairwise comparisons were carried out between libraries to determine the differentially expressed genes. Most resistance-related differentially expressed genes were identified from the comparison of the strains and enriched in pathways for exogenous detoxification including cytochrome P450 and the ABC transporter. Further confirmation came from the weighted gene co-expression network analysis, which indicated that genes in the significant module associated with chlorantraniliprole resistance were enriched in pathways for exogenous detoxification, and that CYP6B6-like represented a hub gene in the “darkred” module. Furthermore, RNAi knock-down of CYP6B6-like increases P. xylostella sensitivity to chlorantraniliprole. Our study thus provides a genetic foundation underlying selection for pesticide resistance and plausible mechanisms to explain fast evolved adaptation through genomic divergence and altered gene expression in insects. 相似文献
18.
Hideyuki Inui Toshimasa Itoh Keiko Yamamoto Shin-Ichi Ikushiro Toshiyuki Sakaki 《International journal of molecular sciences》2014,15(8):14044-14057
Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls (PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation through the food chain from the environment. The authors examined human and rat cytochrome P450 (CYP)-dependent metabolism of PCDDs and PCBs. A number of human CYP isoforms belonging to the CYP1 and CYP2 families showed remarkable activities toward low-chlorinated PCDDs. In particular, human CYP1A1, CYP1A2, and CYP1B1 showed high activities toward monoCDDs, diCDDs, and triCDDs but no detectable activity toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD). Large amino acids located at putative substrate-recognition sites and the F-G loop in rat CYP1A1 contributed to the successful metabolism of 2,3,7,8-tetraCDD. Rat, but not human, CYP1A1 metabolized 3,3'',4,4'',5-pentachlorobiphenyl (CB126) to two hydroxylated metabolites. These metabolites are probably less toxic than is CB126, due to their higher solubility. Homology models of human and rat CYP1A1s and CB126 docking studies indicated that two amino acid differences in the CB126-binding cavity were important for CB126 metabolism. In this review, the importance of CYPs in the metabolism of dioxins and PCBs in mammals and the species-based differences between humans and rats are described. In addition, the authors reveal the molecular mechanism behind the binding modes of dioxins and PCBs in the heme pocket of CYPs. 相似文献
19.
Werner Koehl Shantu Amin Hiroshi Yamazaki Yune-Fang Ueng Tomonuri Tateishi F. Peter Guengerich 《Polycyclic Aromatic Compounds》2013,33(1-4):59-66
The metabolic activation of chrysene, a weak carcinogen found in tobacco smoke, gasoline engine exhaust, and other environmental sources was analyzed in 18 human hepatic and 11 pulmonary microsomal samples. The major metabolites formed were 3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), chrysene-1,2-diol and to lower extents phenols. Chrysene-5,6-diol was found in trace amounts only. All human liver samples formed the proximate carcinogen chrysene-1,2-diol (1.3–5.8 pmol/mg protein/min). Comparable results were seen with pulmonary microsomes, but metabolites were formed to about 10 fold lower extents. Here the most prominent metabolite was chrysene-1,2-diol. Catalytic activities known to be associated with specific cytochrome P450s were determined and correlated with the levels of metabolites formed in each sample. The results of the correlation analysis as well as studies with the inhibitor α-naphthoflavone indicated that hepatic cytochrome P450 1A2 plays a major role in the formation of the proximate carcinogen chrysene-1,2-diol and most of the other metabolites. The formation of metabolites in human lung seems mainly to be due to cytochrome P450 1A1 activity. These results demonstrate that cytochrome-P450 1A mediated metabolic activation processes occur for chrysene in human liver and lung. 相似文献
20.