Environmental Chemistry and Ecotoxicology
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2025
·
IF 8.2
Xin Wan,Geyu Liang,Dayong Wang
The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans , we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents during this process. In citric acid cycle, contents of intermediates were reduced by 0.1–10 μg/L 6-PPDQ. Meanwhile, expression of key enzyme genes ( cts-1 , idh-2 , dlst-1 , and dld-1 ) for citric acid cycle was decreased by 0.1–10 μg/L 6-PPDQ. After 6-PPDQ exposure, citric acid content was reduced by cts-1 RNAi, and NADH content was reduced by idh-2 , dlst-1 , and dld-1 RNAi. Exposure to 6-PPDQ (0.1–10 μg/L) further decreased acetyl CoA and pyruvate contents, and inhibited expression of enzyme genes ( dlat-1 and dld-1 ) governing acetyl CoA synthesis and enzyme genes ( pyk-1 and pyk-2 ) governing pyruvate synthesis. After 6-PPDQ exposure, dlat-1 and dld-1 RNAi reduced contents of acetyl CoA, citric acid, and NADH, and pyk-1 and pyk-2 RNAi reduced contents of pyruvate, citric acid, and NADH. In 6-PPDQ exposed nematodes, cts-1 , idh-2 , dlst-1 , dld-1 , dlat-1 , pyk-1 , and pyk-2 RNAi further caused susceptibility to 6-PPDQ toxicity. Our results suggested 6-PPDQ exposure risk in resulting in damage on citric acid cycle, which was linked to its toxicity induction.
研究领域:
环境毒理学
·
分子生物学
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产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Wenjuan Zhang,Xuerui Ma,Yijia Zhang,Wanjing Tong,Xing Zhang,Yong Liang,Maoyong Song
Bisphenol P (BPP), structurally similar to bisphenol A, is commonly identified in the samples of environment, food, and humans. Unfortunately, very little information is currently available on adverse effects of BPP. The obesogenic effects and underlying mechanisms of BPP on mice were investigated in this study. Compared with the control, high-resolution microcomputed tomography (micro-CT) scans displayed that the visceral fat volume of mice was significantly increased at a dose of 5 mg/kg/day after BPP exposure for 14 days, whereas the subcutaneous fat volume remained unchanged. Nontargeted metabolomic analysis revealed that BPP significantly perturbed the metabolic pathways of mouse livers, and acetyl-CoA was identified as the potential key metabolite responsible for the visceral fat induced by BPP. These findings recommend that a great deal of attention should be paid to the obesogenic properties of BPP as a result of its widely utilized and persistence in the environment.
研究领域:
环境科学
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代谢生物学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
Microbial Cell Factories
·
2016
·Vol. 15
·期 1
·1-9
·
IF 3.744
Yang Jianming,Nie Qingjuan
Background Under aerobic conditions, acetic acid is the major byproduct produced by E. coli during the fermentation. And acetic acid is detrimental to cell growth as it destroys transmembrane pH gradients. Hence, how to reduce the production of acetic acid and how to utilize it as a feedstock are of intriguing interest. In this study, we provided an evidence to produce β-caryophyllene by the engineered E. coli using acetic acid as the only carbon source. Results Firstly, to construct the robust acetate-utilizing strain, acetyl-CoA synthases from three different sources were introduced and screened in the E. coli . Secondly, to establish the engineered strains converting acetic acid to β-caryophyllene, acetyl-CoA synthase (ACS), β-caryophyllene synthase (QHS1) and geranyl diphosphate synthase (GPPS2) were co-expressed in the E. coli cells. Thirdly, to further enhance β-caryophyllene production from acetic acid, the heterologous MVA pathway was introduced into the cells. What’s more, acetoacetyl-CoA synthase (AACS) was also expressed in the cells to increase the precursor acetoacetyl-CoA and accordingly resulted in the increase of β-caryophyllene. The final genetically modified strain, YJM67, could accumulate the production of biomass and β-caryophyllene up to 12.6 and 1.05 g/L during 72 h, respectively, with a specific productivity of 1.15 mg h −1 g −1 dry cells, and the conversion efficiency of acetic acid to β-caryophyllene (gram to gram) reached 2.1 %. The yield of β-caryophyllene on acetic acid of this strain also reached approximately 5.6 % of the theoretical yield. Conclusions In the present study, a novel biosynthetic pathway for β-caryophyllene has been investigated by means of conversion of acetic acid to β-caryophyllene using an engineered Escherichia coli . This was the first successful attempt in β-caryophyllene production by E. coli using acetic acid as the only carbon source. Therefore, we have provided a new metabolic engineering tool for β-caryophyllene synthesis.
研究领域:
生物技术
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代谢工程
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微生物学
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DOI
PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
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2025
·
IF 5.7
Minghao Jiang,Xin Chen,Tianqiao He,Wei Hu,Ning Zhao,Min Liao,Haiqun Cao
Chinese sprangletop ( Leptochloa chinensis (L.) Nees) is among the most economically damaging and disruptive weeds found in rice fields across China, and it exhibits a high degree of cyhalofop-butyl resistance for the past few years. Here, a suspected cyhalofop-butyl-resistant population HFCH5 (R) was collected from a rice field and analyzed to explore the mechanistic basis for its resistance activity. Compared with the susceptible HFLY1 (S) population, this R population exhibited differing levels of resistance to four ACCase-inhibiting herbicides (cyhalofop-butyl (RI = 11.52), fenoxaprop- P -ethyl (RI = 11.05), metamifop (RI = 6.61), and clethodim (RI = 4.06)), although it did exhibit susceptibility to florpyrauxifen-benzyl, tripyrasulfone, pyraclonil, and anilofos. This cyhalofop-butyl resistance in R plants was not effectively mitigated by pre-treatment with the cytochrome P450 inhibitor piperonyl butoxide or the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole. Further analyses of these R plants revealed the substitution of Trp-1999 (TGG) for a Gly residue (GGG) within the ACCase carboxyltransferase domain. When the wild-type and mutated forms of this ACCase protein were subjected to structural modeling while complexed with a range of herbicides with ACCase-inhibiting activity, this Trp-1999-Gly substitution was found to be associated with a slight decrease in the affinity of this protein for a series of ACCase-inhibiting herbicides. A dCAPS marker was developed to aid in the rapid detection of this Trp (TGG)-1999-Gly (GGG) mutation within L. chinensis . Notably, before or after four ACCase-inhibiting herbicides (cyhalofop-butyl, fenoxaprop- P -ethyl, metamifop and clethodim) treatment, ACCase gene expression level of the R plants was not significantly higher (fold change <2, P > 0.05) than that of the S plants. This study is the first report that in grass species, the newly identified ACCase Trp-1999-Gly mutation is associated with ACCase-inhibiting herbicide resistance.
研究领域:
植物学
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遗传学
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农业科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2016
·Vol. 7
·期 1
·1-12
·
IF 11.329
Lv Xiaomei,Wang Fan,Zhou Pingping,Ye Lidan,Xie Wenping,Xu Haoming,Yu Hongwei
Microbial production of isoprene from renewable feedstock is a promising alternative to traditional petroleum-based processes. Currently, efforts to improve isoprenoid production in Saccharomyces cerevisiae mainly focus on cytoplasmic engineering, whereas comprehensive engineering of multiple subcellular compartments is rarely reported. Here, we propose dual metabolic engineering of cytoplasmic and mitochondrial acetyl-CoA utilization to boost isoprene synthesis in S. cerevisiae . This strategy increases isoprene production by 2.1-fold and 1.6-fold relative to the recombinant strains with solely mitochondrial or cytoplasmic engineering, respectively. By combining a modified reiterative recombination system for rapid pathway assembly, a two-phase culture process for dynamic metabolic regulation, and aerobic fed-batch fermentation for sufficient supply of acetyl-coA and carbon, we achieve 2527, mg l −1 of isoprene, which is the highest ever reported in engineered eukaryotes. We propose this strategy as an efficient approach to enhancing isoprene production in yeast, which might open new possibilities for bioproduction of other value-added chemicals.
研究领域:
生物技术
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代谢工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2014
·
IF 2.884
Xiaomei Lv,Wenping Xie,Wenqiang Lu,Fei Guo,Jiali Gu,Hongwei Yu,Lidan Ye
To explore the capacity of isoprene production in Saccharomyces cerevisiae , a rational push-pull-restrain strategy was proposed to engineer the mevalonic acid (MVA) and acetyl-CoA pathways. The strategy can be decomposed into the up-regulation of precursor supply in the acetyl-CoA module and the MVA pathway (push-strategy), increase of the isoprene branch flux (pull-strategy), and down-regulation of the competing pathway (restrain-strategy). Furthermore, to reduce the production cost arising from galactose addition and meanwhile maintain the high expression of Gal promoters, the galactose regulatory network was modulated by Gal80p deletion. Finally, the engineered strain YXM10- ispS-ispS could accumulate up to 37 mg/L isoprene (about 782-fold increase compared to the parental strain) under aerobic conditions with glycerol-sucrose as carbon source. In this way, a new potential platform for isoprene production was established via metabolic engineering of the yeast native pathways.
研究领域:
生物化学
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合成生物学
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代谢工程
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2021
·Vol. 78
·期 3
·1176-1186
·
IF 4.845
Ning Zhao,Minghao Jiang,Qi Li,Quan Gao,Jingxu Zhang,Min Liao,Haiqun Cao
BACKGROUND Chinese sprangletop ( Leptochloa chinensis (L.) Nees) is an invasive grass weed severely infesting rice fields across China. In October 2020, a suspected resistant Leptochloa chinensis population HFFD3 that survived the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide cyhalofop-butyl applied at its field-recommended rate was collected from a rice field in Feidong County, Anhui Province, China. This study aimed to determine the resistance profile of HFFD3 to ACCase inhibitors and to investigate its mechanisms of resistance to cyhalofop-butyl. RESULTS Single-dose testing confirmed that HFFD3 had evolved resistance to cyhalofop-butyl. Two loci encoding plastidic ACCase were each amplified from the susceptible (S) and resistant (R, HFFD3) individual plants. Target gene sequencing and derived cleaved amplified polymorphic sequence assay revealed all the R plants carried a Trp-2027-Leu substitution in their ACCase1,2 copies. Dose–response bioassays revealed that HFFD3 was highly resistant to cyhalofop-butyl and exhibited cross-resistance to metamifop, fenoxaprop- P -ethyl, quizalofop- P -ethyl, and clethodim. Pre-treatment with piperonyl butoxide and 4-chloro-7-nitrobenzoxadiazole considerably reversed the resistance of the R plants to cyhalofop-butyl, by 23% and 43%, respectively. Liquid chromatography–tandem mass spectrometry analysis suggested the metabolic rates of cyhalofop-butyl were significantly faster in the R than in the S plants. CONCLUSION This study confirmed the first case of an arable weed species featuring cross-resistance to ACCase-inhibiting herbicides due to a novel Trp-2027-Leu mutation of ACCase . Target gene mutation and cytochrome P450s- and glutathione- S -transferases-involved enhanced metabolism may have simultaneously participated in the resistance of HFFD3 population to cyhalofop-butyl.
研究领域:
植物学
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遗传学
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农药科学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2024
·
IF 3.8
Minghao Jiang,Xumiao Wang,Wei Hu,Zezhou Wang,Huaiji Guan,Ning Zhao,Min Liao,Haiqun Cao
BACKGROUND Chinese sprangletop [ Leptochloa chinensis (L.) Nees] control is threatened by resistance to acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. In this study, a L. chinensis population, HFLJ18, that survived cyhalofop-butyl [aryloxyphenoxypropionate (APP) herbicide, CyB] treatment was collected from a rice field in Lujiang County, Anhui Province, China. This study aimed to evaluate the susceptibility of HFLJ18 to herbicides with different modes-of-action and investigate the potential mechanisms of resistance to CyB. RESULTS The HFLJ18 population exhibited high levels of resistance to CyB (10.92-fold) and showed resistance to the ACCase inhibitors metamifop (4.63-fold) and fenoxaprop- P -ethyl (8.39-fold), but was susceptible to clethodim, pinoxaden, florpyrauxifen-benzyl, oxadiazon and pretilachlor. Target gene sequencing revealed a novel Trp-to-Gly substitution at codon position 2027 of ACCase in the resistant plants. Molecular docking revealed that the spatial structure of ACCase changed significantly following the substitution, as indicated by reduced H-bonds. A newly derived cleaved amplified polymorphic sequence (dCAPS) marker was subsequently developed to detect the Trp-2027-Gly mutation in the ACCase of L. chinensis . Additionally, pretreatment with the cytochrome P450 (P450) inhibitor piperonyl butoxide (PBO) and the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) did not reverse resistance to CyB, suggesting that nontarget-site resistance mechanisms were not involved in CyB resistance in the HFLJ18 population. CONCLUSION Overall, the resistance to CyB in the HFLJ18 population derived from the mutation of ACCase gene, and to the best of our knowledge, this is the first report of the ACCase Trp-2027-Gly mutation conferring resistance to ACCase-inhibiting herbicides in grass species. © 2024 Society of Chemical Industry.
研究领域:
植物科学
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分子生物学
·
农业化学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 7
·1-17
·
IF 8.1
Wang Yuying,Su Kunqi,Wang Chang,Deng Tao,Liu Xiaofeng,Sun Shiqi,Jiang Yang,Zhang Chunfeng,Xing Baocai,Du Xiaojuan
Chemotherapeutic efficacy is seriously impeded by chemoresistance in more than half of hepatocellular carcinoma (HCC) patients. However, the mechanisms involved in chemotherapy-induced upregulation of chemoresistant genes are not fully understood. Here, this study unravels a novel mechanism controlling nuclear acetyl-CoA production to activate the transcription of chemoresistant genes in HCC. NAT10 is upregulated in HCC tissues and its upregulation is correlated with poor prognosis of HCC patients. NAT10 is also upregulated in chemoresistant HCC cells. Targeting NAT10 increases the cytotoxicity of chemotherapy in HCC cells and mouse xenografts. Upon chemotherapy, NAT10 translocates from the nucleolus to the nucleus to activate the transcription of CYP2C9 and PIK3R1 . Additionally, nuclear acetyl-CoA is specifically upregulated by NAT10. Mechanistically, NAT10 binds with ACLY in the nucleus and acetylates ACLY at K468 to counteract the SQSTM1-mediated degradation upon chemotherapy. ACLY K468-Ac specifically accumulates in the nucleus and increases nuclear acetyl-CoA production to activate the transcription of CYP2C9 and PIK3R1 through enhancing H3K27ac. Importantly, K468 is required for nuclear localization of ACLY. Significantly, ACLY K468-Ac is upregulated in HCC tissues, and ablation of ACLY K468-Ac sensitizes HCC cells and mouse xenografts to chemotherapy. Collectively, these findings identify NAT10 as a novel chemoresistant driver and the blockage of NAT10-mediated ACLY K468-Ac possesses the potential to attenuate HCC chemoresistance.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2019
·Vol. 75
·期 12
·3175-3183
·
IF 3.255
Ning Zhao,Lu'an Ge,Yanyan Yan,Shuang Bai,Dandan Wang,Weitang Liu,Jinxin Wang
BACKGROUND Asia minor bluegrass ( Polypogon fugax Nees ex Steud.) is an invasive grass species severely infesting wheat and canola fields in China. In May 2017, a suspected resistant P. fugax population AHHY that survived fenoxaprop- P -ethyl applied at its field-recommended rate was collected from a wheat field in Huaiyuan County, Anhui Province, China. This study aimed to determine the resistance profile of AHHY to acetyl-CoA carboxylase (ACCase) inhibitors and to investigate its mechanisms of resistance to fenoxaprop. RESULTS Single-dose testing indicated that the AHHY population had evolved resistance to fenoxaprop. The partial carboxyltransferase domain of ACCase in P. fugax was amplified and compared. Four loci encoding plastidic ACCase were isolated from both the resistant and sensitive individuals. Combining gene sequencing with the derived cleaved amplified polymorphic sequence assay, we found that 100% of the plants of AHHY carried Trp-1999-Ser mutation in their ACCase1,1–2 allele. Whole-plant dose–response bioassay indicated that AHHY was highly resistant to fenoxaprop and pinoxaden (resistance index (RI) ≥ 10) with low resistance to clodinafop-propargyl, sethoxydim, and clethodim (2 ≤ RI < 5). Pre-treatment with piperonyl butoxide largely reduced (55%) the weed's resistance to fenoxaprop. Both basal and fenoxaprop-induced glutathione S -transferases activities toward 1-chloro-2, 4-dinitrobenzene were significantly higher in resistant plants than in susceptible plants. CONCLUSION This study revealed that P. fugax had multiple alleles encoding plastidic ACCase, and reported for the first time the occurrence of Trp-1999-Ser mutation and non-target-site resistance in this species. Fenoxaprop resistance in AHHY plants was conferred by target-site mutation and P450s-involved enhanced metabolism. © 2019 Society of Chemical Industry
研究领域:
植物学
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植物生理学
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分子生物学
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杂草科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Shendong Zhou,Nana Ma,Meijuan Meng,Guangjun Chang,Xiangzhen Shen
Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on β-hydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.
研究领域:
兽医学
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分子生物学
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药理学
·
动物生理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Xue Bai,Shuling Wang,Qin Zhang,Yuhan Hu,Jiawei Zhou,Lianhui Men,Dengyu Li,Jing Ma,Qiuhui Wei,Mengdie Xu,Xiaopu Yin,Tianyuan Hu
Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein tSmKSL1-CfTPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.
研究领域:
生物技术
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代谢工程
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）