JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Wenjing Liu,Xiaoxiang Hu,Linghao Fang,Yujie Cai
Spermidine is a naturally occurring polyamine with multiple biological activities and potential food and agricultural applications. However, sustainable and scalable spermidine production has not yet been attained. In this study, a homospermidine synthase (HSS) from Pseudomonas frederiksbergensis (PfHSS) capable of catalyzing the synthesis of spermidine from 1,3-diaminopropane and putrescine was identified based on multiple sequence alignment using Blastochloris viridis HSS (BvHSS) as a template. The optimal reaction pH and temperature for purified PfHSS were determined to be 8.5 and 45 °C, respectively, and K+ was able to promote the enzyme activity. Further analysis of the structural and functional relationships through molecular docking and molecular dynamics simulation indicates that glutamic acid at position 359 is the essential residue for the enzyme-catalyzed synthesis of spermidine. The whole-cell catalytic reaction yielded 1321.4 mg/L spermidine and 678.2 mg/L of homospermidine. This study presents a novel, promising, and sustainable biological method for producing spermidine.
研究领域:
生物化学
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合成生物学
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食品科学
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农业科学
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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
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代谢生物学
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营养学
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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
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分子生物学
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药理学
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PubMed
高影响因子
Aging-US
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2020
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IF 4.831
Ting-Ting Xu,Han Li,Zhao Dai,George K. Lau,Ben-Yue Li,Wen-Li Zhu,Xiao-Qi Liu,Hao-Fei Liu,Wei-Wu Cai,Shui-Qing Huang,Qi Wang,Shi-Jie Zhang
The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of MFN1, MFN2, DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, NLRP3, IL-18, IL-1β) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including NGF, PSD95and PSD93 and BDNF in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.
研究领域:
神经科学
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衰老
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药理学
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DOI
PubMed
高影响因子
Synthetic and Systems Biotechnology
·
2024
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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
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合成生物学
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PubMed
高影响因子
Bioactive Materials
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2026
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IF 20.3
Weiwei Yu,Xiang Li,Xufang Liu,Xinyi Hao,Wen Qin,Guoqing Qi,Gaopeng Dang,Ziyuan Tian,Shiyin Jin,Conrado Aparicio,Kaiyan Wang,Wen Niu,Lina Niu
Oral ulceration is a prevalent mucosal disorder, and its healing process is frequently hampered by poor local drug retention and inadequate mucosal adhesion. However, the underlying pathological mechanisms remain incompletely elucidated. In this study, transcriptomic sequencing revealed that ferroptosis serves as a key driver of oral ulcer progression. To address the limitations of conventional formulations in the wet and dynamic oral environment, we constructed an asymmetrically adhesive, ferroptosis-targeting, spermidine (SPD)-functionalized Janus hydrogel microneedle system (MN-HTSO-C). This system was fabricated via chemical grafting and dynamic Schiff base crosslinking, enabling targeted drug delivery into mucosal tissues. By specifically delivering SPD, this system effectively inhibited ferroptosis, reduced reactive oxygen species (ROS) accumulation, reprogrammed the local immune microenvironment, and thereby promoted angiogenesis and epithelial regeneration. Our work not only identifies a novel pathological mechanism but also proposes an integrated therapeutic strategy that combines targeted delivery, immunomodulation, and ferroptosis inhibition, providing a new direction for the treatment of oral ulcers and other ferroptosis-related mucosal diseases.
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高影响因子
Regenerative Biomaterials
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2023
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IF 6.7
Zhang Songbai,Jia Yuanbo,Liu Jingyi,Feng Fan,Wei Zhao,Zhang Min,Xu Feng
Periodontitis can cause irreversible defects in the periodontal ligament (PDL), the regeneration of which is the major obstacle to the clinical treatment of periodontitis. Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration. However, existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium, which may have been shown as an important role in tissue regeneration. Meanwhile, the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive. In this study, we developed a bi-crosslinking viscoelastic hydrogel (Alg-PBA/Spd) by integrating phenylboronic acid-modified alginate with anti-inflammatory agent (spermidine) through borate ester and B–N coordination bonds, where spermidine will be released with the degradation of the hydrogel. Alg-PBA/Spd hydrogel is biocompatible, injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking. We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage. Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.
研究领域:
牙科材料
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组织工程
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再生医学
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生物材料科学
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Tianqi Nie,Hengyu Liu,Zhengwen Fang,Yilu Zheng,Ruhe Zhang,Xiaojun Xu,Sixi Liu,Jun Wu
Immunotherapy as an alternative treatment strategy for B-cell lymphoma is undesirable because of tumor heterogeneity and immune surveillance. Spermidine (SPM), as a regulator of the tumor microenvironment (TME), can facilitate the release of damage-associated molecular patterns (DAMPs) from cancer cells, promote immune recognition, and thus alleviate immune surveillance in the TME. Hence, in this work, self-assembled spermidine-based metal-immunopeptide nanocomplexes (APP-Fe NCs; APP is anti-programmed death ligand-1 peptide) with pH-responsive release kinetics were prepared via the flash nanocomplexation (FNC) technique based on the noncovalent interaction between APP-SPM-dextran (DEX) and sodium tripolyphosphate (TPP) and coordination between Fe3+ and TPP. An in vitro study suggested that APP-Fe NCs effectively induce strong oxidative stress and mitochondrial dysfunction and subsequently lead to ferroptosis in cells by interfering with homeostasis in lymphoma cells. Further investigation on lymphoma mice models demonstrated that APP-Fe NCs effectively inhibited the growth and liver metastasis of lymphomas. Mechanistically, by triggering ferroptosis in tumor tissues, these spermidine-containing APP-Fe NCs efficiently facilitated the release of DAMPs and ultimately reshaped TME to enhance immunotherapy efficacy in lymphoma. Combined with its good histocompatibility and facile preparation technique, this pH-responsive APP-Fe NCs with regulation on TME may hold potential for cascade amplification on the combinative immunotherapy of lymphoma in the clinic.
研究领域:
癌症研究
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纳米技术
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免疫学
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药学
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DOI
PubMed
高影响因子
PLoS One
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2023
·Vol. 18
·期 8
·e0289563
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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
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生理学
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PubMed
高影响因子
Gut Microbes
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2020
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IF 7.74
Lingyan Ma,Yinhua Ni,Zhe Wang,Wenqing Tu,Liyang Ni,Fen Zhuge,Aqian Zheng,Luting Hu,Yufeng Zhao,Liujie Zheng,Zhengwei Fu
Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. However, the mechanism of spermidine on obesity remains unclear. Here, we show that spermidine intake is negatively correlated with obesity in both humans and mice. Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function. Microbiota depletion compromises function, while transplantation of spermidine-altered microbiota confers protection against obesity. These changes might partly be driven by an SCFA-producing bacterium, Lachnospiraceae NK4A136 group, which was decreased in obese subjects and subsequently increased by spermidine. Notably, the change of Lachnospiraceae NK4A136 group is significantly correlated with enhanced gut barrier function induced by spermidine. Our results indicate that spermidine supplementation may serve as a viable therapy for obesity.
研究领域:
营养学
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微生物学
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代谢学
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胃肠病学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2019
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IF 5.399
Xiaoman Yang,Shuang Lin,Yongxia Jia,Fazal Rehman,Shaohua Zeng,Ying Wang
The Lycium ruthenicum (Lr) fruit is a widely used nutritional food that contains various bioactive components such as anthocyanin and spermidine derivatives. In the present study, ultra-high-performance liquid chromatography with tandem mass spectrometry was utilized to profile the metabolic dynamics of four developmental stages of Lr fruit. A total of 49 compounds, including anthocyanin, alkaloids, hydroxycinnamic acid derivatives, flavonoids, and amino acids, were tentatively identified. Principal component analysis distinguished the fruit at four developmental stages using 15 (9 were tentatively identified) potential marker compounds. Pearson correlation analysis suggested that anthocyanin and spermidine derivative hexoses had a strong positive correlation coefficient. A glucosyltransferase (HG27071) was confirmed to glucosylate both anthocyanidin and spermidine derivative in vitro . Our results provide insight into the metabolic linkages among bioactive components in Lr fruits. The glucosyltransferase identified in this study will promote its potential use in functional foods and natural pigment resources.
研究领域:
植物科学
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生物化学
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食品科学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
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IF 13.6
Zheng Deng,Xirui Wu,Tianhao Huang,Huiyuan Chen,Zhuochao Wu,Li Liu,Yuqian Liu,Chunjie Wang,Zijian Xiong,Zhuang Liu,Guangbao Yang
Intracellular polyamine metabolic homeostasis is closely linked to therapeutic outcomes in cancer. However, their intrinsic antitumor mechanisms have not been fully clarified. Herein, we demonstrate that the catabolism of spermine (Spm) and spermidine (Spd) mediated by polyamine oxidase directly generates two potent cytotoxic metabolites, namely acrolein and hydrogen peroxide. These metabolites act synergistically to trigger a marked elevation in intracellular reactive oxygen species (ROS), which in turn activate the caspase-1/GSDMD and caspase-3/GSDME signaling pathways, ultimately driving tumor cells into pyroptosis. Based on these findings, we develop a phenylboronic acid-functionalized sodium alginate-based hydrogel controlled-release system (Alg-PBA/Spd). This platform achieves sustained Spd release through coordination interactions and markedly inhibits tumor growth by inducing pyroptosis. Further studies demonstrate that the Alg-PBA/Spd hydrogel synergizes with radiotherapy (RT) to enhance radiosensitivity in an orthotopic breast cancer model and inhibit pulmonary metastasis. Moreover, this hydrogel enables co-delivery of αPD-L1 with sustained release, which significantly improves the response rate of immune checkpoint blockade therapy by inducing pyroptosis and remodeling the tumor immune microenvironment. Overall, this study not only elucidates a previously unrecognized mechanism underlying polyamine metabolism-driven pyroptosis but also offers a versatile platform to enhance the efficacy of RT and immunotherapy.
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高影响因子
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