Synthetic and Systems Biotechnology
·
2024
·
IF 4.4
Wenjing Liu,Xiaoxiang Hu,Yi Yan,Yujie Cai
Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases. Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme catalysis. Based on sequence-structure-function relationships, we engineered the widely studied homospermidine synthase from Blastochloris viridis ( Bv HSS) and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine. The specific activities of Bv HSS and the mutants D361E and E232D + D361E (E232D-D) were 8.72, 46.04 and 48.30 U/mg, respectively. The optimal pH for both mutants was 9.0, and the optimal temperature was 50 °C. Molecular docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket, promoting stable spermidine production. Conversely, mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance, facilitating substrate entry into the active pocket and enhancing spermidine generation. In whole-cell catalysis lasting 6 h, D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine, respectively. This study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.
研究领域:
生物化学
·
合成生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Dan Feng,Jian Zhang,Huanmin Niu,Xiaoxue Zheng,Mengqi Jia,Qiqi Lu,Jing Wang,Wenxue Guo,Qi Sun,Huiqing Yuan,Hongxiang Lou
The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe 2+ levels in vitro . Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe 2+ , is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Xin Ji,Huilong Guo,Qiao Tang,Dong Ma,Wei Xue
Antitumor efficacy of methotrexate (MTX) is seriously limited due to its poor water solubility, nonspecific tumor distribution and low bioavailability. To overcome these obstacles, polyspermine (PSP) conjugated with MTX and folic acid (FA) as a novel targeted prodrug was designed and has been successfully synthesized using the amidation reaction. The strong hydrophilic properties of PSP made MTX well dispersed in water and the cellular uptake study indicated that the presence of FA enhanced uptake of the FA-PSP-MTX in folate receptor (FR) over-expressing human nasopharyngeal carcinoma HNE-1 cells. 1 H NMR spectra and UV–Vis spectral analysis were carried out to confirm the MTX and FA content in FA-PSP-MTX, respectively. In CCK-8 assay and apoptosis analysis, the prodrug showed significantly enhanced anticancer efficacy than free MTX in HNE-1 cells. These results suggested that the prodrug has the potential for targeted delivery of MTX into cancer cells to improve its anti-tumor efficacy.
研究领域:
药理学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Zekun Shi,Yongning Wu,Xue Zhang,Yanyan Gao,Luqin Qiao,Qin Hou,Minglin Wang
Fluorescent cuprous iodide (CuI)-based coordination polymers (CuI-CPs) were widely used in the sensor field for high selectivity and sensitivity. Here, a new CuI-CP fluorescent probe was fabricated for the detection of spermine, spermidine and cysteine with dual-mode, which was capable of both convenient colorimetric analysis and ratiometric fluorescent detection. The fluorescence of CuI-CP solution was quenched and the solution changed from white to purple upon addition of spermine or spermidine, while the solution changed from white to yellow for cysteine. This probe exhibited selective, sensitive, rapid and linear response to spermine, spermidine and cysteine with a limit of detection of 0.57, 1.06 and 1.18 μM, respectively. Furthermore, cellulose acetate was used as the matrix to fabricate intelligent fluorescent film for real-time and visual monitoring the freshness of pork samples based on distinct fluorescence changes under UV light. This work realized a rapid, efficient, and profitable method for visually evaluating food quality.
研究领域:
分析化学
·
材料科学
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
ELECTROANALYSIS
·
2021
·Vol. 33
·期 9
·2016-2024
·
IF 3.223
Yongliang Guo,Lili Tian,Jiangming Wu,Yang Wu,Yongmei Liu,Jie Du,Xiaoquan Lu
In this study, we found that spermine (SPM) could enhance electrochemiluminescence (ECL) intensity of Au−Ag bimetallic nanoclusters (Au−Ag BNCs) with triethylamine (TEA) as a co-reactant. An ECL sensor was fabricated to detect SPM, which contained Au−Ag BNCs as ECL emitters and conductive hydrogel containing polyaniline-amino trimethylene phosphonic acid (PANI-ATMP) as an immobilizing matrix. The increased ECL intensity of SPM was linear with the logarithm of concentrations of SPM in the range of 1 pM to 10 μM with high selectivity, excellent stability, and the limit of detection is 0.11 pM (S/N=3). This sensor realized the detection of SPM in urine samples, which was fast and economic, possessing potential applications for SPM detection in clinical and bioanalysis.
研究领域:
分析化学
·
生物医学
✓ 已验证
产品关联
DOI
高影响因子
BMC PLANT BIOLOGY
·
2017
·Vol. 17
·期 1
·1-16
·
IF 3.964
Huang Yutao,Lin Cheng,He Fei,Li Zhan,Guan Yajing,Hu Qijuan,Hu Jin
Background The low seed vigor and poor field emergence are main factors that restricting the extension of sweet corn in China. Spermidine (Spd) plays an important role in plant growth and development, but little is known about the effect of Spd on sweet corn seed germination. Therefore the effect of exogenous Spd on seed germination and physiological and biochemical changes during seed imbibition of Xiantian No.5 were investigated in this study.Results Spd soaking treatment not only improved seed germination percentage but also significantly enhanced seed vigor which was indicated by higher germination index, vigor index, shoot heights and dry weights of shoot and root compared with the control; while exogenous CHA, the biosynthesis inhibitor of Spd, significantly inhibited seed germination and declined seed vigor. Spd application significantly increased endogenous Spd, gibberellins and ethylene contents and simultaneously reduced ABA concentration in embryos during seed imbibition. In addition, the effects of exogenous Spd on H2O2 and MDA productions were also analyzed. Enhanced H2O2 concentration was observed in Spd-treated seed embryo, while no significant difference of MDA level in seed embryo was observed between Spd treatment and control. However, the lower H2O2 and significantly higher MDA contents than control were detected in CHA-treated seed embryos.Conclusion sThe results suggested that Spd contributing to fast seed germination and high seed vigor of sweet corn might be closely related with the metabolism of hormones including gibberellins, ABA and ethylene, and with the increase of H2O2 in the radical produced partly from Spd oxidation. In addition, Spd might play an important role in cell membrane integrity maintaining.
研究领域:
植物生理学
·
农业科学
✓ 已验证
DOI
PubMed
高影响因子
Sensors & Diagnostics
·
2025
·
IF 4.1
Teody Gumabat,Jeanne Phyre Lagare Oracion,Jolina Fedelis,Ethel Keleste,Rey Capangpangan,Noel Lito Sayson,Gerard Dumancas,Arnold Alguno,Felmer Latayada
Spermine, a key biogenic amine indicating food freshness, is typically detected using costly and time-consuming chromatographic methods. This study introduces a more efficient, eco-friendly alternative—a label-free colorimetric sensing platform using gold nanoparticles (AuNPs) functionalized with 11-mercaptoundecanoic acid and capped with an N-hydroxysuccinimide (NHS)-ester. Transmission electron microscopy revealed monodisperse, spherical AuNPs (13 nm), with an increase in size upon functionalization. Fourier transform infrared spectra confirmed successful functionalization. The hydrodynamic size of the AuNPs increased from 17.26 nm to 2167 nm, and the zeta potential shifted from −48.86 mV to −35.59 mV. The platform takes advantage of the selective interaction between spermine and NHS-ester-functionalized AuNPs, inducing nanoparticle aggregation, as shown by a red shift in surface plasmon resonance (SPR). UV-vis spectroscopy demonstrated a robust linear correlation (R2 = 0.958) between spermine concentration (1.0–4.0 μM) and nanoparticle aggregation index, with a limit of detection (LOD) of 0.77 μM. The sensor also exhibited high reproducibility in pork extract matrices (coefficient of variation <5%) and selectivity for spermine amid various interfering analytes. Its eco-friendly design and rapid response time position it as a viable tool for real-time spermine monitoring in food spoilage, offering comparable performance metrics to traditional chromatographic techniques while addressing sustainability concerns.
研究领域:
生物化学
·
食品安全
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2017
·
IF 1.74
Jing Wang,TongMing Li,Linquan Zang,Xuediao Pan,Sujun Wang,Yanyan Wu,Guixiang Wang
Apigenin is a nonmutagenic flavonoid that has antitumor properties. Polyamines are ubiquitous cellular polycations, which play an important role in the proliferation and differentiation of cancer cells. Highly regulated pathways control the biosynthesis and degradation of polyamines. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the metabolism, and spermidine/spermine-N1-Acetyl transferase (SSAT) is the rate-limiting enzyme in the catabolism of polyamines. In the current study, the effect of increasing concentrations of apigenin on polyamine levels, ODC and SSAT protein expression, mRNA expression, cell proliferation and apoptosis, and the production of reactive oxygen species (ROS) was investigated in SW620 colon cancer cells. The results showed that apigenin significantly reduced cell proliferation, decreased the levels of spermidine and spermine, and increased previously downregulated putrescine contents. Apigenin also enhanced SSAT protein and mRNA levels and the production of reactive oxygen species in SW620 cells, though it had no significant effect on the levels of ODC protein or mRNA. Apigenin appears to decrease the proliferation rate of human SW620 cells by facilitating SSAT expression to induce polyamine catabolism and increasing ROS levels to induce cell apoptosis.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-15
·
IF 15.7
Ma Yanfei,Zhong Yifan,Tang Wenjie,Valencak Teresa G.,Liu Jingliang,Deng Zhaoxi,Mao Jiangdi,Liu Daren,Wang Shanshan,Wang Yuhao,Wang Haifeng
Metabolic syndrome (MetS) is a difficult-to-manage disease that poses a significant risk to human health. Here, we show that the supplementation of Lactobacillus reuteri ZJ617 ameliorates symptoms of MetS in mice induced by the high-fat diet. L. reuteri ZJ617 modulates host metabolism by interacting with the microbiome, resulting in the production of spermidine synthesized by the microbiota. L. reuteri ZJ617 serves as a source of substrates for the microbiota to synthesize spermidine, hence preventing the decline of bacteria responsible for spermidine production. Spermidine treatment mimics the metabolic effects of L. reuteri ZJ617, whereas pharmacological inhibition of spermidine biosynthesis in mice abolishes these benefits. Our findings reveal the mechanism by which L. reuteri ZJ617 alleviates MetS symptoms and provide support for its potential use as a probiotic for promoting metabolic health.
研究领域:
微生物学
·
代谢生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2023
·Vol. 18
·期 8
·e0289563
·
IF 3.7
Dongdong Cao,Yutao Huang,Gaofu Mei,Sheng Zhang,Huaping Wu,Tiyuan Zhao
Chilling stress is an important constraint for kale seed germination and seedlings establishment. It is vital to develop an effective approach to enhance kale seed germination ability under chilling stress. The present study reported that spermidine (Spd) could improve seed chilling tolerance in two kale cultivars ‘Nagoya’ (MGW) and ‘Pigeon’ (BB) during germination. The results showed that MGW was cold tolerant with a 90.67% germination percentage (GP) under chilling stress, while BB was cold sensitive with a 70.67% GP under chilling stress. Spd content in MGW and BB seeds during seed germination were up-regulated and down-regulated by chilling stress, respectively. Besides, chilling stress apparently decreased the gibberellin (GA) and ethylene (ET) contents, while increased the levels of abscisic acid (ABA) and reactive oxygen species (ROS) in MGW and BB seeds during germination. Exogenous Spd application increased GA, ET contents and decreased ABA content through regulating the gene expressions of metabolic-related enzymes, thus effectively alleviating the low temperature damage on kale seed germination. Besides, Spd significantly increased the activities of superoxide dismutase (SOD) and peroxidase (POD), and reduced the levels of hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 · - ). The present study demonstrated that endogenous Spd metabolism plays an important role in kale seed germination under chilling stress. The effect of exogenous Spd on the metabolism of endogenous Spd, GA, ABA, ET and antioxidant enzymes might be the important reason for promoting the kale seed vigor at low temperature.
研究领域:
植物学
·
生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Lina Geng,Chirun Lin,Guojian Pan,Yusen Yang,Lixing Wang,Shengming Huang,Zhiyu Zhou,Haoran Yin,Xiaoyi Wu
Spermine, a natural polyamine, plays important roles in regulating growth, protein synthesis and antioxidant capacity of organisms. The purpose of this study was to assess the effects of dietary spermine supplementation on growth, protein synthesis and antioxidant capacity in hybrid grouper ( Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). Seven isoproteic, isoenergetic, and isolipidic diets containing different levels of exogenous spermine were formulated and fed to juvenile fish for 8 weeks. At the end of the feeding trial, nine fish were randomly selected from each tank and subjected to ammonia nitrogen stress for 57 h. The results showed that with increasing dietary spermine levels, the daily feed intake significantly decreased ( P < 0.05), and significant cubic variations of protein efficiency ratio, protein productive value and dorsal muscle / body weight ratio were observed. There were no significant differences in serum growth hormone, insulin-like growth factor 1, spermine, and spermidine levels among the groups. The expression levels of target of rapamycin ( tor ), eukaryotic initiation factor 5 A ( eif 5 a ) and TOR phosphorylation level were also affected by dietary spermine. For gut histology analysis, only villus height of foregut was changed. After the ammonia‑nitrogen stress, there was a cubic correlation between spermine levels and cumulative mortality rate. The serum catalase, heme oxygenase 1 concentrations and the expression levels of NAD( P )H: quinone oxidoreductase 1 ( nqo 1) exhibited a cubic variation as dietary spermine levels increased. In summary, the optimal dietary spermine level for maximum percentage weight gain was estimated to be 19.9 mg/kg dry matter.
研究领域:
水产养殖学
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Jin Long Zhang,Xiao Wei Zhang,Bing Yuan,Heng Zhang,Xing Zhi Wang,Hao Wang,Hong Wei Zhao
Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load chemotherapy medication, nitrogen mustard (NM), via forming a direct host–guest complex, as this helps to decrease the cytotoxicity of NM on normal mammary epithelial cells. Attributed to the stronger complexation ability of CP6A for endogenous spermine (SPM) than for NM, the complexed NM could be competitively released from the CP6A cavity via replacement with SPM. This chemotherapy strategy performed well in vitro and in vivo for SPM-overexpressed cancers. In comparison with free NM, antitumor efficiency of NM/CP6A was significantly enhanced, which originated from the synergistic effect of competitive release of NM and simultaneous trapping of SPM. This strategy might guide expansion to other first-line antitumor agents to improve therapeutic efficacy and decrease side effects, thereby replenishing the possibilities of supramolecular chemotherapy.
研究领域:
药学
·
肿瘤学
·
超分子化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）