INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiang Pu,Jiahua Zhang,Jinwei He,Zhihui Ai,Xiaoxue He,Xiaojun Zhou,Shiyuan Tong,Xinyue Dai,Qiqi Wu,Jiayu Hu,Jingshu He,Hanguang Wang,Wei Wang,Jinqiu Liao,Li Zhang
The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O -methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4′-OH group. CaFOMT2 possesses sequential O -methyltransferase activity for the 4′-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMT s evolved independently and that their ancestral genes are different from that of the known Ca10OMT . This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata .
研究领域:
植物生物化学
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分子生物学
·
植物化学
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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Yin Zhen-Hua,Liu Xiao-Peng,Wang Jin-Mei,Xi Xue-Feng,Zhang Yan,Zhao Rui-Lin,Kang Wen-Yi
Pleurotus placentodes, a fungus, belongs to the Pleurotaceae family. The aim of the present study was to characterize the structure of a novel polysaccharide from fruiting bodies of P. placentodes (PPp-W) and evaluate its anticoagulant activity in vitro. The high-performance liquid chromatography and GC–MS analysis indicated that PPp-W with a molecular weight of 27.4 kDa was mainly composed of mannose (17.56%), glucose (6.37%), galactose (44.89%), and fucose (1.22%) with a certain amount of 3-O-methyled galactose. SEM, XRD, and AFM combined with Congo red test revealed that PPp-W was an irregular curly sheet with triple-helix conformation. The FT-IR, methylation, and nuclear magnetic resonance analysis indicated that PPp-W contained→6)-α-D-Galp-(1→, →6)-3-O-Me-α-D-Galp-(1→and →2, 6)-α-D-Galp-(1→ as main chain, partially substituted at O-2 and O-6 by non-reducing ends of β-D-Manp-(1→ and β-L-Fucp-(1→ with a small amount of α-1,3-linked-Glcp in backbone. PPp-W could significantly prolong APTT (12.9 ± 0.42 s, p < 0.001) and thrombin time (39.9 ± 0.28 s, p < 0.01) compared with the control group (11.45 ± 0.071 s and 38.05 ± 0.21 s), which showed that PPp-W had anticoagulant activity. These studies suggested that PPp-W was a 3-O-methylated heteroglycan and might be suitable for functional foods and natural drugs as an anticoagulant ingredient, which provided a basis for the application of polysaccharides from P. placentodes.
研究领域:
真菌学
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生物化学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Genetics
·
2025
·
IF 2.8
Minglu Zhang,Jianbo He,Rao Fu,Guojian Bao,Yijun Lu,Zechuan Zhang,Jiawu Yan,Jialu Ding,Fei Yang,Beicheng Sun
Introduction: Small nucleolar RNA (snoRNA) mediates RNA modifications, including 2′-O-methylation (Nm) and pseudouridine (Ψ), which has been proven to impact tumor progression. However, the role of snoRNA in the epigenetics of tumors remains poorly understood due to the lack of sufficiently effective experimental methods to identify snoRNA targets. Here, we identified SNORD13H, a C/D box snoRNA, as being downregulated in hepatocellular carcinoma (HCC), and its low expression was associated with HCC development.Methods: To elucidate specific roles of SNORD13H in HCC, we used a comprehensive array of methodologies, including flow cytometry, xenograft mouse model, reverse transcription at low dNTP concentration followed by PCR (RTL-P) assay, and surface sensing of translation (SUnSET) assay.Results: In this study, we first demonstrated that reduced SNORD13H serves as a biomarker for HCC, facilitating cellular proliferation. SNORD13H mediates 2′-O-methylations of 18S rRNA and RAS mRNA, thereby enhancing translation efficiency and regulating RAS protein levels in HCC. The diminution of SNORD13H activates the RAS pathway, contributing to the progression of HCC.Discussion: Our study establishes SNORD13H as a dual-function regulator in HCC progression. Furthermore, our findings indicate that SNORD13H is detectable in plasma, highlighting its potential utility in tumor screening.
研究领域:
分子生物学
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癌症研究
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遗传学
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表观遗传学
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RNA修饰
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产品关联
DOI
PubMed
高影响因子
TETRAHEDRON
·
2017
·
IF 2.651
Zhenyu Tian,Kun Meng,Yanhong Shi,Naixia Zhang,Xuehui Liu,Hongwei Jin,Yongmin Zhang,Lihe Zhang,Demin Zhou,Sulong Xiao
A newly synthesized hexavalent oleanolic acid/per- O -methylated α -cyclodextrin conjugate shows significant differences in NMR spectra with previously synthesized analogs. Characterization of the product by 1 H NMR, 13 C NMR, COSY, HSQC , HMBC , TOCSY , NOE, and ROESY experiments were performed. Detailed investigations revealed that the compound has two conformations in solution and the ratio of them was 1:1. Further variable-temperature NMR study revealed that the two conformations were stable at temperature range of 273–323 K in CDCl 3 solution.
研究领域:
有机化学
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药物化学
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DOI
高影响因子
Synthetic and Systems Biotechnology
·
2024
·
IF 4.4
Moli Sang,Qingyu Yang,Jiawei Guo,Peiyuan Feng,Wencheng Ma,Wei Zhang
A novel sub-class of S -adenosyl- l -methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from Streptomyces purpurascens, it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4- O -methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4- O -methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.
研究领域:
微生物学
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生物化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Wei Li,Chong Qiao,Jing Pang,Guolin Zhang,Yinggang Luo
Amaryllidaceae alkaloids are unique benzylphenethylamine derivatives that comprise of more than 600 members with a huge chemical diversity. Most of them showed interesting bioactivities, for instance, galanthamine (GAL) is clinically used for Alzheimer's disease treatment. All Amaryllidaceae alkaloids had been thought to be derived from 4′- O -methylnorbelladine originated from norbelladine catalyzed by norbelladine 4′- O -methyltransferase (N4OMT). Herein we mined the transcriptome datasets of Lycoris radiata , a GAL-producing plant. LrOMT was cloned, overexpressed in Escherichia coli , and purified to homogeneity. Bioinformatics analysis and enzymatic activity assays revealed that LrOMT is an S-adenosylmethionine-dependent Class I OMT. LrOMT exhibited both para - and meta - O -methylation activities toward norbelladine to give 4′- and 3′- O -methylnorbelladine. Twenty-four analogues, including the proposed biosynthetic intermediates, were introduced to investigate the substrate scope of LrOMT and it showed that the aromatic substrates should have two vicinal hydroxyl groups. The LrOMT-catalyzed O -methylation preference is dependent on the properties of the binding group of the substrates. The transcription levels of LrOMT were positively associated with the accumulation of the Amaryllidaceae alkaloids and the biosynthetic intermediates in L. radiata . The present work revealed that LrOMT catalyzes multiple O -methylation reactions and its characterization will be helpful to uncover novel biosynthetic genes for Amaryllidaceae alkaloids biosynthesis.
研究领域:
植物生物化学
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酶学
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分子生物学
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生药学
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产品关联
DOI
PubMed
高影响因子
EMBO JOURNAL
·
2024
·
IF 9.4
ChenJiajia,LiYucong,WangYan,WangHui,YangJiaqi,PanXue,ZhaoYun,XuHao,JiangPenglei,QianPengxu,WangHongwei,XieZhi,LeiKai
Tissue homeostasis and regeneration involve complex cellular changes. The role of rRNA modification-dependent translational regulation in these processes remains largely unknown. Planarians, renowned for their ability to undergo remarkable tissue regeneration, provide an ideal model for the analysis of differential rRNA regulation in diverse cell types during tissue homeostasis and regeneration. We investigated the role of RNA 2’-O-methyltransferase, Fibrillarin (FBL), in the planarian Schmidtea mediterranea and identified two FBL homologs: Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2). Both are essential for planarian regeneration, but play distinct roles: fbl-1 is crucial for progenitor cell differentiation, while fbl-2 is important for late-stage epidermal lineage specification. Different 2’-O-methylation patterns were observed upon fbl-1 and fbl-2 knockdown, suggesting their roles in translation of specific mRNA pools during regeneration. Ribo-seq analysis further revealed differing impacts of fbl-1 and fbl-2 knockdown on gene translation. These findings indicate divergent roles of the duplicate fbl genes in specific cell lineage development in planarians and suggest a role of rRNA modifications in translational regulation during tissue maintenance and regeneration.
研究领域:
发育生物学
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分子生物学
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再生生物学
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产品关联
DOI
PubMed
高影响因子
ChemSusChem
·
2021
·Vol. 15
·期 3
·e202102538
·
IF 8.928
Yuen Wai Lui,Bun Chan,Matthew Y. Lui
Graphical Circular Economy : A sustainable methylation process is developed using only inexpensive methanol and bio-based chemicals with a very easy workup and purification procedure. Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O -methylated phenols and benzoic acids, and mono- C -methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide‘s neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Brønsted base.
研究领域:
有机化学
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绿色化学
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可持续发展
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催化
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化学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Boyang Cheng,Xindang Chu,Ruiwen Liu,Xinyuan Ma,Mengyang Wang,Jiayi Zhang,Pingxuan Jiao,Qianqian Gao,Wenxiao Ma,Yongmin Zhang,Chuanke Zhao,Demin Zhou,Sulong Xiao
Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
研究领域:
药理学
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肿瘤学
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药物化学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2016
·Vol. 40
·期 10
·8928-8934
·
IF 3.277
Ren-Jie Li,Jian-He Xu,Yue-Cai Yin,Nicolas Wirth,Jiang-Meng Ren,Bu-Bing Zeng,Hui-Lei Yu
Developing a detailed understanding of the reactivity of self-sufficient Type IV P450 monooxygenases, four types of O-methylated substrates were designed as probes, including monoterpenes, cycloalkanes, aromatic compounds and steroids, and the efficiency of their oxyfunction was determined using a colorimetric assay which was based on the reaction between the enzymatic demethylation product, formaldehyde, and Purpald dye. The activity-based fingerprints of new P450RpMO, P450ArMO and P450CtMO (CYP116B members) indicated that CYP116B P450s preferentially oxidize substrates with aromatic components. Moreover, the hydroxylated products were detected based on the preference results. This rapid and efficient strategy, when coupled with GCMS, enables the exploration of the reactivity of other CYP116B members.
研究领域:
生物化学
·
酶学
·
代谢工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）