BIORESOURCE TECHNOLOGY
·
2015
·
IF 4.494
Guanyi Wang,Di Huang,Yong Li,Jianping Wen,Xiaoqiang Jia
In this work, wheat bran (WB) was utilized as feedstock to synthesize fumaric acid by Rhizopus oryzae . Firstly, the pretreatment process of WB by dilute sulfuric acid hydrolysis undertaken at 100 °C for 30 min offered the best performance for fumaric acid production. Subsequently, through optimizing the seed culture medium, a suitable morphology (0.55 mm pellets diameter) of R. oryzae was obtained. Furthermore, a metabolic-based approach was developed to profile the differences of intracellular metabolites concentration of R. oryzae between xylose (the abundant sugar in wheat bran hydrolysate (WBH)) and glucose metabolism. The xylitol, sedoheptulose 7-phosphate, ribulose 5-phosphate, glucose 6-phosphate, proline and serine were responsible for fumaric acid biosynthesis limitation in xylose fermentation. Consequently, regulation strategies were proposed, leading to a 149% increase in titer (up to 15.4 g/L). Finally, by combinatorial regulation strategies the highest production was 20.2 g/L from WBH, 477% higher than that of initial medium.
研究领域:
生物工程
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代谢生物学
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DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-12
·
IF 5.3
Zhou Hongyan,Hu Dingxin,Zhao Xian,Qin Siyuan,Nong Qiyao,Tian Yuan,Zhang Zunjian,Dong Haijuan,Zhang Pei,Xu Fengguo
Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
研究领域:
肿瘤学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 3.7
Ying Li,Yu Zeng,Shuo Zhao,Zhen Wang,Li Chen,Kequan Chen
Pyruvate, a pivotal metabolite in the glycolytic pathway, typically confronts substantial barriers to its natural accumulation within microbial cells. This study successfully facilitated the natural accumulation of pyruvate in Actinobacillus succinogenes 130Z by fine-tuning the oxidation-reduction potential (ORP) in the fermentation milieu. A mechanistic exploration revealed that the accumulation of pyruvate was optimized when ORP conditions favorably modulated pyruvate kinase activity and concurrently suppressed succinate dehydrogenase activity. By integrating the influence of metal ions on enzymatic functions with an innovative aluminum ion-mediated ORP control strategy, we achieved a pyruvate yield of 27.54 g/L over 20 hours, which constitutes an 89.54% increase compared to the baseline. Additionally, the production rate of pyruvate reached 1.38 g/L·h. This investigation not only elucidates the metabolic underpinnings that facilitate the natural enrichment of glycolytic intermediates in Actinobacillus succinogenes 130Z but also lays a robust theoretical foundation for the industrial-scale fermentation of pyruvate. Moreover, the capability to efficiently and rapidly concentrate essential platform metabolites within the glycolytic pathway is of paramount significance, potentially propelling forward the research and synthesis of various downstream metabolic products.
研究领域:
微生物学
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生物化学
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工业发酵
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DOI
高影响因子
Microbial Biotechnology
·
2024
·Vol. 17
·期 4
·e14455
·
IF 4.8
Xuke Yang,Jichao Yang,Mengyu Lyu,Yaqiong Li,Anqi Liu,Bang Shen
Toxoplasma gondii is a zoonotic parasite infecting humans and nearly all warm-blooded animals. Successful parasitism in diverse hosts at various developmental stages requires the parasites to fine tune their metabolism according to environmental cues and the parasite's needs. By manipulating the β and γ subunits, we have previously shown that AMP-activated protein kinase (AMPK) has critical roles in regulating the metabolic and developmental programmes. However, the biological functions of the α catalytic subunit have not been established. T. gondii encodes a canonical AMPKα, as well as a KIN kinase whose kinase domain has high sequence similarities to those of classic AMPKα proteins. Here, we found that Tg KIN is dispensable for tachyzoite growth, whereas Tg AMPKα is essential. Depletion of Tg AMPKα expression resulted in decreased ATP levels and reduced metabolic flux in glycolysis and the tricarboxylic acid cycle, confirming that Tg AMPK is involved in metabolic regulation and energy homeostasis in the parasite. Sequential truncations at the C-terminus found an α-helix that is key for the function of Tg AMPKα. The amino acid sequences of this α-helix are not conserved among various AMPKα proteins, likely because it is involved in interactions with Tg AMPKβ, which only have limited sequence similarities to AMPKβ in other eukaryotes. The essential role of the less conserved C-terminus of Tg AMPKα provides opportunities for parasite specific drug designs targeting Tg AMPKα.
研究领域:
寄生虫学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF LEUKOCYTE BIOLOGY
·
2025
·
IF 3.1
Song Zichen,Wang Jiangrong,Zheng Zhihang,He Zhixiang,Xun Jingna,Gu Ling,Shen Yinzhong,Chen Jun
Inhibiting the metabolic activity of CD4+ T cells can effectively reduce HIV infection. Mitochondria, as critical organelles in eukaryotic metabolism, play a significant role in the progression of many diseases. The change of mitochondrial dynamics is an important process of mitochondrial regulation of cell metabolic activity. However, it remains uncertain whether regulating mitochondrial dynamics is a viable approach to reducing HIV infection. In this study, we demonstrated that promoting mitochondrial fusion in Jurkat cells through treatment with the mitochondrial fusion promoter M1 and the dynamin-related protein 1 (Drp1) inhibitor Mdivi1 conferred resistance to single-round VSVG-HIVNL4-3-GFP viral infection. Targeted metabolomics analysis revealed and subsequently confirmed the potential involvement of citrate in reducing HIV infection, which has been subsequently verified. And we found that plasma citrate level was negatively associated with HIV disease progression. Multi-omics results showed that citric acid leads to a decrease in the level of nucleotide metabolism in Jurkat cells. In conclusion, increased citrate levels resulting from mitochondrial fusion significantly impair the ability of HIV to infect cells, which may due to regulate nucleotide metabolism
研究领域:
免疫学
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病毒学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Zu-Wen Ye,Qi-Yue Yang,Dong-Hua Yang,Qiao-Hong Lin,Xiao-Xia Liu,Feng-Qin Li,Fang-Fang Yan,Ping Luo,Si Qin,Fang Wang
Introduction: Obesity, a global health challenge, is characterized by excessive fat accumulation and associated metabolic disorders. The ZhiZhu decoction, a traditional Chinese herbal formula consisting of Citrus aurantium L. (ZS, ZhiShi in Chinese) and Atractylodes macrocephala Koidz (BZ, Baizhu in Chinese), is widely recognized in clinics for its gastrointestinal regulatory effects.Methods: The chemical composition of ZS-BZ essential oil (ZBEO) was characterized using gas chromatography-mass spectrometry (GC-MS). Concurrently, we conducted in vitro investigations using HepG2 hepatoma cells to evaluate its anti-lipid deposition potential. To further elucidate the anti-obesity mechanisms, an in vivo model was established through high-fat diet (HFD)-induced obese rats, followed by transdermal ZBEO administration. Systemic analyses were performed integrating serum metabolomic profiling via UPLC-QTOF-MS and gut microbiota dynamics assessment through 16S rRNA gene sequencing.Results: ZBEO, rich in atractylon, D-limonene, and γ-elemene and shown to reduce lipid accumulation. Transdermal ZBEO administration in obese rats led to significant weight loss and improved serum metabolic indexes related to the POMC/CART signaling pathway. Additionally, ZBEO altered gut microbiota, enhancing beneficial bacteria and affecting metabolic pathways linked to obesity.Discussion: We discovered that ZBEO exerts a significant influence on obesity by modulating key biological processes, including glucose metabolism, lipid metabolism, and the composition of gut microbiota.
研究领域:
药理学
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代谢生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Rui Bai,Wei Chen,Xudong Zhou,Junpeng Li,Yi He,Yong Xiao,Feng Zhao
Bacitracin is renowned for its broad-spectrum antimicrobial activity and low propensity to induce resistance. However, how to achieve efficient bacitracin production remains a significant challenge. In this study, we developed a Bacillus licheniformis -CdSe biohybrid system that operates under sunlight, employing dual regulatory strategies of "increasing incomes" and "cutting expenses" to achieve efficient bacitracin production. For the increasing incomes strategy: CdSe converted solar energy into photoelectrons, providing B. licheniformis with additional energy and accelerating intracellular energy metabolism; For the cutting expenses strategy: Light exposure induced a metabolic pathway rearrangement in B. licheniformis , suppressing the pathway of pulcherrimin synthesis, thereby conserving energy and redirecting resources toward bacitracin synthesis. By integrating these two regulatory strategies, the bacitracin yield exhibited a remarkable increase, achieving a cumulative concentration of 390.9 mg·L −1 within 24 h. Comprehensive analyses, including biochemistry, electrochemistry, proteomics, and transcriptomics, demonstrated that light optimizes energy allocation by suppressing metabolic byproducts in B. licheniformis , thereby enhancing selectivity for the target product. CdSe efficiently harvested solar energy, accelerating intracellular regeneration of ATP and NAD( P )H, and promoting the production of precursor amino acids, ultimately boosting bacitracin synthesis. This study provides insight into how to design microbe-semiconductor biohybrid systems for the sustainable synthesis of high-value chemicals.
研究领域:
微生物学
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生物技术
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光化学
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合成生物学
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产品关联
DOI
高影响因子
Cell Chemical Biology
·
2017
·
IF 0
Yongliang Xia,Feifei Luo,Yanfang Shang,Peilin Chen,Yuzhen Lu,Chengshu Wang
Summary Cordycepin (COR) and pentostatin (PTN) are adenosine analogs with related bioactivity profiles as both mimic adenosine and can inhibit some of the processes that are adenosine dependent. Both COR and PTN are also natural products and were originally isolated from the fungus Cordyceps militaris and the bacterium Streptomyces antibioticus , respectively. Here, we report that not only is PTN produced by C. militaris but that biosynthesis of COR is coupled with PTN production by a single gene cluster. We also demonstrate that this coupling is an important point of metabolic regulation where PTN safeguards COR from deamination by inhibiting adenosine deaminase (ADA) activity. ADA is not inhibited until COR reaches self-toxic levels, at which point ADA derepression occurs allowing for detoxification of COR to 3′-deoxyinosine. Finally, we show that using our biosynthetic insights, we can engineer C. militaris to produce higher levels of COR and PTN.
研究领域:
真菌学
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生物化学
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药物开发
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DOI
ADVANCED FUNCTIONAL MATERIALS
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2025
·
IF 19
Hong Chen,Peng Lei,Tianming Wang,Ting Li,Minjuan Zhong,Lili Zhang,Xianting Sun,Hao Zhou,Yue Liu,Weihua Liao,Yanlan Liu
Manipulating metabolic rewiring in cancer cells has become a central focus in cancer treatment. However, the intricate, yet not fully elucidated, adaptability of cancer metabolism frequently undermines the effectiveness of such interventions. Here, a novel cascade metabolic regulation system is presented by manipulating the mitochondria-cytosol metabolic networks to disrupt multipath energy replenishment in cancer. Specifically, multienzymatic Mn-LDH nanodiscs are synthesized, which not only impair energy metabolism in mitochondria by triggering mitochondrial dysfunction via self-cascade catalysis, but also show the activity of blocking the compensatory energy metabolism from cellular glycogen. Concurrently, vessel embolization is combined to obstruct the carbon sources essential for both glycolysis in cytosol and the tricarboxylic acid (TCA) cycle in mitochondria, while simultaneously fostering an environment conducive to Mn-LDH catalysis. This dual-pronged regulation strategy induced ATP exhaustion and apoptosis in cancer cells, leading to remarkably enhanced antitumor efficacy in orthotopic liver tumor rabbit models compared to a standard clinical embolization formulation for advanced liver tumors. Moreover, comprehensive mechanism studies across cellular and animal models confirmed that this strategy effectively blocked multifaceted metabolic adaptations within the mitochondria and cytosol of cancer cells. Overall, this work offers a promising platform for metabolic intervention and provides important insights into cancer biology and management.
研究领域:
生物化学
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分子生物学
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肿瘤学
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产品关联
DOI
高影响因子
Cell Reports
·
2025
·
IF 6.9
Li Chai,Chaoqun Li,Xuefeng Wang,Yanyang Qin,Hemin Sun,Jie Du,Liu Yang,Dongmei Hu,Jianan Xiong,Zhiyuan Zhao,Rong Gong,Tao Wu,Meng Wu,Meng Nie,Jialin Gao,Jihui Jia,Chengjiang Gao,Wei Zhao,Huan Zhou,Dongwei Kang,Mutian Jia
Perturbation of energy metabolism is an essential feature during infection and inflammation. TANK-binding kinase 1 (TBK1) is crucial for initiating the innate immune response against viral infection, although aberrant and ongoing TBK1 activation induces excessive production of type I interferons (IFN-I). Nonetheless, the mechanisms whereby energy metabolism controls TBK1 activation remain unclear. Here, we elucidate a mechanism linking energy metabolism to the inhibition of TBK1-induced IFN-I responses via the immune response gene 1 (IRG1)-itaconic acid axis. Mechanistically, itaconic acid and its derivatives alkylated TBK1 at Cys605, thereby disrupting TBK1 dimerization and rapid activation. IRG1, the enzyme that catalyzes itaconic acid production, is upregulated during late-phase viral infection and acts as a feedback regulator to restrain TBK1 activity. We developed itaconic acid-based compounds ITA-5/ITA-9 as alternative TBK1 inhibitors. ITA-5/ITA-9 effectively limited excess IFN-I-mediated hyperinflammation. These findings provide a promising therapeutic strategy for treating diseases mediated by aberrant TBK1 activation.
研究领域:
免疫学
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分子生物学
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代谢调控
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先天免疫
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病毒感染
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信号转导
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药物开发
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Jiaying Jin,Xiaogang Wang,Yu Zhang,Liangjie Ba,Su Xu,Lingshuai Meng,Xiaohong Kou,Sen Cao
Blueberry aroma is a key determinant of fruit quality and market value. However, the mechanisms underlying its formation during ripening remain poorly understood. This study utilized the highbush blueberry cultivar ‘ Legacy ’ and employed an integrated approach combining E -nose, GC–MS, GC-IMS, and transcriptomics to systematically analyze the formation and changes in VOCs as well as the underlying molecular mechanisms throughout fruit ripening. The results revealed that during the entire fruit ripening process, VOCs were predominantly composed of alcohols, aldehydes, and terpenoids. Key compounds, including hexanol, linalool and geraniol, progressively accumulated. Furthermore, the combination of GC–MS and GC-IMS provided a more comprehensive profile of the volatile composition in blueberry fruit. Transcriptomic analysis further elucidated its metabolic regulatory mechanisms: 1) Terpenoid biosynthesis is co-regulated by the MAV and MEP pathways, with the MEP pathway playing a dominant role in monoterpene biosynthesis; 2) Fatty acid metabolism generates C6 aldehydes via LOX2S, while upregulation of ADH gene expression significantly enhances the conversion of aldehydes to alcohols. This study provides valuable theoretical foundations for flavor development during blueberry ripening.
研究领域:
植物生物学
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食品科学
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分子生物学
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代谢组学
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农业生物技术
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产品关联
DOI
PubMed
高影响因子
PLANT AND CELL PHYSIOLOGY
·
2024
·
IF 3.9
Yun Cholil,Pak Solme,Pang Yulin,Phyon Jong Min,Yao Liuyang,Guo Xiaorui,Kim Cholung,Ma Songsu,Ri Tongchol,Pak Ryongho,Wang Huimei
The adventitious root (AR) culture of Atractylodes chinensis is an efficient platform for sustainable production of its sesquiterpenoid compounds (atractylon and β-eudesmol). However, their limited accumulation levels need an effective elicitation approach, and the present study solved this problem using methyl jasmonate (MeJA) as an elicitor. The effects of its treatment concentration and duration on metabolite production were investigated. The ARs treated with 100 µM MeJA for seven days increased atractylon and β-eudesmol by 3.64- and 1.90-fold, respectively, compared with the control. This study further performed transcriptome analysis to explore the transcriptional regulation mechanism of the MeJA elicitation. A total of 124,464 unigenes were identified in A. chinensis ARs, of which 3,568 genes were upregulated and 3,864 genes were downregulated under the MeJA treatment. The MeJA treatment activated the endogenous JA biosynthesis and signaling pathways and sesquiterpenoid biosynthesis. The MeJA treatment more significantly activated the MEP pathway than the MVA pathway. In addition, 14 genes encoding terpene synthase were identified to be significantly upregulated. A total of 2,700 transcription factors (TFs) were identified in A. chinensis ARs, of which Tify, MYB, and MADS were significantly enriched under the MeJA treatment. We predicted a new antagonistic interaction between MYC2 and CPP TFs, which was significantly regulated by the MeJA treatment. The results of real-time quantitative PCR and enzyme activity assays proved the reliability of the transcriptome data. This study will help improve the in vitro production system of A. chinensis sesquiterpenoids and understand the transcriptional regulation mechanism of MeJA elicitation.
研究领域:
植物学
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药用植物研究
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分子生物学
·
次生代谢研究
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产品关联
DOI
PubMed
高影响因子
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