Synthetic and Systems Biotechnology
·
2024
·
IF 4.4
Shanquan Liang,Zi He,Dan Liu,Shaoqing Yang,Qiaojuan Yan,Zhengqiang Jiang
2′-Fucosyllactose (2′-FL) is one of the important functional oligosaccharides in breast milk. So far, few attempts on biosynthesis of 2′-FL by the salvage pathway have been reported. Herein, the salvage pathway enzyme genes were introduced into the E. coli BL21star(DE3) for synthesis of 2′-FL. The 2′-FL titer increased from 1.56 to 2.13 g/L by deleting several endogenous genes on competitive pathways. The α-1,2-fucosyltransferase (WbgL) was selected, and improved the 2′-FL titer to 2.88 g/L. Additionally, the expression level of pathway enzyme genes was tuned through optimizing the plasmid copy number. Furthermore, the spatial distribution of WbgL was enhanced by fusing with the MinD C-tag. After optimizing the fermentation conditions, the 2′-FL titer reached to 7.13 g/L. The final strain produced 59.22 g/L of 2′-FL with 95% molar conversion rate of lactose and 92% molar conversion rate of fucose in a 5 L fermenter. These findings will contribute to construct a highly efficient microbial cell factory to produce 2′-FL or other HMOs.
研究领域:
生物化学
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微生物学
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合成生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
·
2024
·Vol. 75
·期 2
·91
·
IF 2
Yu Bai,Chenwei Dai,Nini Chen,Xiuhong Zhou,Hua Li,Qinghua Xu,Yong Xu
Hepatocellular carcinoma has high fatality and poor prognosis. For curing hepatocellular carcinoma, the demand for effective therapeutic reagents with low toxicity is urgent. Herein, we investigated plasma-activated medium, an emerging reagent obtained via irradiation of cell-free medium with cold atmospheric plasma. Plasma-activated medium exerts inhibitory effect on many types of tumor cells with little toxicity to non-cancerous cells. In present study, we verified the tumor-specific inhibition of plasma-activated medium on hepatocellular carcinoma cell lines. Under the effect of plasma-activated medium, oxidative stress, mitochondrial dysfunction, and loss of intracellular NAD + and ATP were detected inside cells, suggesting an energy depletion. Through investigating the salvage pathway which synthesizes NAD + and maintains the respiratory chain in hepatocellular carcinoma, we found that the energy failure was resulted by the blockage of the salvage pathway. Moreover, nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway, was determined as an important target to be inactivated by the effect of plasma-activated medium. Additionally, the blockage of the salvage pathway activates AMPKα and suppresses mTOR pathway, which reinforces the cell growth inhibition. Overall, our findings demonstrated that the disruption of functions of nicotinamide phosphoribosyltransferase and the salvage pathway contribute to the tumor-specific cytotoxicity of plasma-activated medium.
研究领域:
肿瘤学
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细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2021
·
IF 31.745
Ling-jie Huang,Xin-tao Mao,Yi-yuan Li,Dan-dan Liu,Ke-qi Fan,Rong-bei Liu,Ting-ting Wu,Hao-li Wang,Yu Zhang,Bing Yang,Cun-qi Ye,Jiang-yan Zhong,Ren-jie Chai,Qian Cao,Jin Jin
Summary Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
研究领域:
免疫学
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胃肠病学
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代谢组学
·
系统生物学
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DOI
PubMed
高影响因子
iMeta
·
2024
·
IF 23.7
Hao Zhang,Jiawan Wang,Jianghua Shen,Siqi Chen,Hailong Yuan,Xuan Zhang,Xu Liu,Ying Yu,Xinran Li,Zeyu Gao,Yaohui Wang,Jun Wang,Moshi Song
Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia–reperfusion (I/R) injury, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis ( B. infantis ), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R-induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro-inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen-glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R-induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury. Graphical In this study, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis ( B. infantis ), exhibited cardioprotective effects against myocardial ischemia–reperfusion (I/R) injury, which was recapitulated by its metabolite inosine. Specifically, inosine suppressed cardiac inflammation by reducing the production of pro-inflammatory cytokines and decreasing the numbers of dendritic cells and natural killer cells after I/R. Additionally, inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate generation through the purine salvage pathway in stressed myocytes and in I/R-injured mouse hearts. Collectively, our findings indicate that B. infantis or its metabolite inosine exerts pleiotropic cardioprotective effects against I/R, suggesting prophylactic therapeutic options for acute ischemic cardiac injury. Highlights Bifidobacterium infantis , a well-known probiotic, exhibits prophylactic cardioprotective effects against myocardial I/R injury. The cardioprotective effects of Bifidobacterium infantis are recapitulated by its metabolite inosine. Inosine treatment suppresses cardiac inflammation by reducing the production of pro-inflammatory cytokines and decreasing the numbers of dendritic cells and natural killer cells after I/R. Inosine treatment attenuates cell death by serving as an alternative carbon source for adenosine triphosphate generation through the purine salvage pathway in stressed myocytes and in I/R-injured mouse hearts.
研究领域:
心血管疾病
·
微生物组
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免疫学
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代谢组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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