Biotechnology for Biofuels and Bioproducts
·
2024
·Vol. 17
·期 1
·1-10
·
IF 3.3
Wang Lijuan,Deng Yongdong,Gao Jianjie,Wang Bo,Han Hongjuan,Li Zhenjun,Zhang Wenhui,Wang Yu,Fu Xiaoyan,Peng Rihe,Yao Quanhong,Tian Yongsheng,Xu Jing
Background The demand for melatonin is increasing due to its health-promoting bioactivities such as antioxidant and sleep benefits. Although melatonin is present in various organisms, its low content and high extraction cost make it unsustainable. Biosynthesis is a promising alternative method for melatonin production. However, the ectopic production of melatonin in microorganisms is very difficult due to the low or insoluble expression of melatonin synthesis genes. Hence, we aim to explore the biosynthesis of melatonin using Escherichia coli as a cell factory and ways to simultaneously coordinated express genes from different melatonin synthesis pathways. Results In this study, the mXcP4H gene from Xanthomonas campestris , as well as the HsAADC , HsAANAT and HIOMT genes from human melatonin synthesis pathway were optimized and introduced into E. coli via a multi-monocistronic vector. The obtained strain BL7992 successfully synthesized 1.13 mg/L melatonin by utilizing L-tryptophan ( l -Trp) as a substrate in a shake flask. It was determined that the rate-limiting enzyme for melatonin synthesis is the arylalkylamine N-acetyltransferase, which is encoded by the HsAANAT gene. Targeted metabolomics analysis of l -Trp revealed that the majority of l -Trp flowed to the indole pathway in BL7992, and knockout of the tnaA gene may be beneficial for increasing melatonin production. Conclusions A metabolic engineering approach was adopted and melatonin was successfully synthesized from low-cost l -Trp in E. coli . This study provides a rapid and economical strategy for the synthesis of melatonin.
研究领域:
微生物学
·
代谢工程
·
生物技术
✓ 已验证
DOI
高影响因子
Chinese Journal of Natural Medicines
·
2026
·Vol. 24
·期 1
·59-72
·
IF 4.9
Yang Lin,Zhengmeng Jiang,Zhilu Yu,Tianqing Huang,Wanyu Gui,Ziyuan Wang,Fei Li,Pingting Xiao,Changyin Li,Ehu Liu
Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from Magnolia officinalis bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased Akkermansia muciniphila (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites in vitro . Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON’s clinical applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2014
·
IF 3.511
Xiaojuan Yang,Qingxin Han,Yange Zhang,Jiang Wu,Xiaoliang Tang,Chunxu Dong,Weisheng Liu
Two aptasensors based on graphene oxide (GO) and molecular beacon were designed for the detection of L-tryptophan (L-Trp) using L-Trp aptamer (Trp3a-1). The fluorescein (FAM) labeled Trp3a-1 was absorbed by GO, which resulted in the fluorescence quenching , and exhibiting minimal background fluorescence. Upon the addition of L-Trp, Trp3a-1 was not absorbed quickly. This effect allows for a quantitative assay of L-Trp over the concentration range of 10–500 μM and with a detection limit of 6.84 μM. However, due to the unspecific adsorption of GO, the GO based aptasensor can׳t be applied in complex matrixes. In respect of molecular beacon based aptasensor, FRET between Trp3a-1 labeled with FAM and CS-Trp3a-1 labeled with BHQ-1(black hole quencher-1) which is partially complementary with the aptamer was used to detect L-Trp. L-Trp binding could induce the disassociation of CS-Trp3a-1, resulted in the enhancement of fluorescence in solution. With an excellent linear relationship in 10–500 μM and a detection limit of 6.97 μM in 25% serum, the aptasensor is expected to be improved for the detection of free L-Trp in other complex samples.
研究领域:
生物化学
·
分析化学
·
医学检测
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2012
·Vol. 137
·期 12
·2840-2845
·
IF 4.23
Daixin Ye,Liqiang Luo,Yaping Ding,Bingdi Liu,Xiao Liu
A novel Co3O4 nanoparticles-decorated graphene (GR) composite was synthesized by electro-deposition and characterized by scanning electron micrographs, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and transmission electron microscopy. Then, amperometric biosensors based on a Co3O4 nanoparticles-decorated GR composite modified glassy carbon electrode (GCE) were developed for the sensitive determination of L-tryptophan (Trp). The direct electrooxidation behaviors of Trp on the Co3O4/GR/Nafion/GCE were carefully investigated by cyclic voltammetry and square wave voltammetry. The results indicated that Trp showed an increase of the oxidation peak current with a negative shift of the oxidation peak potential compared with that on the bare GCE. Under optimum conditions, the proposed biosensor can be applied to the quantification analysis of Trp with a wide linear range covering 0.05–10 μM (R = 0.996) and a low detection limit of 0.01 μM. The experimental results also showed that the sensor exhibited good reproducibility, long-term stability as well as high selectivity. Moreover, the novel biosensor for the detection of Trp in a real amino acid sample with satisfactory results has been proved.
研究领域:
分析化学
·
生物传感技术
·
纳米材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Haifeng Hu,Wenting Zhang,Huilong Wang,Shengpeng Zhang,Shaozhen Wang,Yuewu Xie
Introduction Cisplatin (CIS)-induced nephrotoxicity is a dose-limiting adverse effect that hinders its clinical efficacy. Artesunate (ART) exerts well-documented anti-inflammatory and anti-oxidative effects, but its potential efficacy against CIS-induced nephrotoxicity remains poorly elucidated. Methods The renoprotective effects of ART were evaluated in a murine CIS-induced nephrotoxicity model and human HK-2 renal tubular epithelial cells. Renal function, histopathological injury, inflammation, and oxidative stress were evaluated. Untargeted renal metabolomics and transcriptomics were integrated to identify potential pathways, followed by targeted biochemical and molecular validation. Indoxyl sulfate rescue experiments were performed to investigate the functional relationship between tryptophan metabolism and ferroptosis. Results ART treatment significantly ameliorated CIS-induced renal dysfunction, as evidenced by reduced SCr and BUN levels and attenuated histopathological damage. These functional improvements were accompanied by marked suppression of pro-inflammatory cytokines and restoration of redox balance. Integrated renal metabolomic and transcriptomic analyses revealed that ART exerts its protective effects primarily through modulation of tryptophan metabolism and ferroptosis pathway. Subsequent validation confirmed that ART inhibited ferroptosis by reducing Fe 2+ accumulation, downregulating ACSL4 and FTL, and upregulating GPX4 and xCT. In HK-2 cells, indoxyl sulfate partially counteracted the cytoprotective and anti-ferroptotic effects of ART. Moreover, ART did not diminish CIS’s antineoplastic effect in human cancer cells. Conclusion These findings demonstrate that ART alleviates CIS-induced nephrotoxicity by restoring tryptophan metabolic homeostasis and suppressing ferroptosis, positioning ART as a promising therapeutic candidate for preventing nephrotoxicity in patients undergoing CIS chemotherapy.
✓ 已验证
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2022
·Vol. 6
·期 19
·2859-2868
·
IF 8.683
Ming Liu,Ran Cen,Ji-Hong Lu,Tie-Hong Meng,Chun-Rong Li,Carl Redshaw,Timothy J. Prior,Zhu Tao,Xin Xiao
Fluorescent nitrogen and fluorine doped carbon dots (CDs) were prepared by a hydrothermal method using levofloxacin (LVFX) and cucurbit[6]uril (Q[6]) as the nitrogen and carbon sources, respectively. Decomposition of LVFX occurred at elevated temperature affording N,N′-desethylene levofloxacin hydrochloride (N,N′-DLH). The crystal structure of the resulting inclusion complex N,N′-DLH@Q[6]·[CdCl4]2(H3O)·9H2O was determined, where N,N′-DLH is protonated on each of the terminal nitrogens and the quinone functionality is a quinol which forms an intramolecular hydrogen bond to the carboxylic acid. The synthesized N,N′-DLH containing Q[6]-CDs emitted intense blue fluorescence with high photostability and exhibited stability at high ionic strength. In particular, the original rigid macrocyclic skeletons of these hosts were retained during the fabrication process, which helps in uniquely distinguishing them from other reported CDs. Meanwhile, the performance of the Q[6]-CDs was characterized using fluorescence and NMR spectroscopies. Subsequently, using the obtained Q[6]-CDs, an efficient sensing method for L-tryptophan (L-Trp) and capecitabine (CAP) has been developed based on macrocyclic host–guest chemistry. Under applicable conditions, the detection limits for L-Trp and CAP were calculated to be 5.13 × 10−8 M and 1.48 × 10−8 M, respectively.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2021
·
IF 4.464
Tong Li,Yuanyuan Wang,Xianwen Kan
A novel electrochemical chiral sensor was constructed for the discrimination of Tryptophan (Trp) by the modification of Au@Pt bimetallic nanoparticles, poly(cysteine) (PL-Cys), and Cu 2+ -modified β-cyclodextrin (Cu 2 -β-CD) on the surface of glassy carbon electrode. The constructed sensor was characterized by transmission electron microscopy, infrared spectroscopy, UV–vis adsorption spectra, and the electrochemical experiments. The modified Au@Pt endowed the sensor with high surface area and good conductivity. The electropolymerized PL-Cys facilitated the loading of Cu 2 -β-CD based on the electrostatic interaction. As a chiral selector, Cu 2 -β-CD enabled the sensor to effectively identify the Trp enantiomers based on the host–guest interaction with a high the oxidation peak current ratio (I L /I D, I L and I D were the oxidation peak currents of l -Trp and d -Trp measured on the sensor, respectively) of 2.38. Under the optimized conditions, I L /I D increased with the increase of l -Trp in the raceme solution, which was further employed for the detection of Trp in serum samples with satisfactory results. With the good selectivity, stability, and reproducibility, the present electrochemical sensor can be used for the simple, rapid, and efficient chiral recognition and real samples determination.
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2021
·Vol. 12
·期 20
·10184-10195
·
IF 5.396
Zhenyang Gu,Wenlong Pei,Yonghua Shen,Lijuan Wang,Jun Zhu,Yi Zhang,Shengxian Fan,Qian Wu,Lei Li,Zhan Zhang
Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that Akkermansia muciniphila (Akk), a promising probiotic, could protect against colitis via the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between Akk and three Trp metabolites. Live Akk, pasteurised Akk and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live Akk, pasteurised Akk and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live Akk, pasteurised Akk and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised Akk significantly elevated the serum levels of indole acrylic acid (IA). In addition, live Akk, pasteurised Akk and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including CYP1A1, IL-10 and IL-22, suggesting that Akk could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Junzhi,Lin Binyan,Zhang Ying,Hu Xiaochao,Liu Tongtong,Liu E-Hu,Liu Shijia
Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored.Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice.Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels.Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway.Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 9
·1336
·
IF 4.7
Hongchao Wang,Yuan He,Danting Dang,Yurong Zhao,Jianxin Zhao,Wenwei Lu
Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p< 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance ofAnaeroplasma,Akkermansia, andRuminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.
研究领域:
免疫学
·
微生物学
·
呼吸系统疾病
·
代谢组学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Pengfei Ren,Biqian Wei,Wanting Qin,Qingjuan Tang,Yuming Wang,Changhu Xue
This study utilized in vitro colonic fermentation to examine the impact of astaxanthin on the microbial catabolism of tryptophan. Astaxanthin significantly altered the gut microbiota and raised the tryptophan catabolism metabolite levels in an in vitro human colonic fermentation system. To eliminate the influence of substrate availability, we conducted in vitro colonic fermentation of the gut microbiota of astaxanthin-domesticated mice. We observed that the capacity of astaxanthin-domesticated gut microbiota to catalyze the conversion of tryptophan to indole and derivatives was considerably augmented. Astaxanthin significantly increased the relative abundance of Akkermansia, Ruminococcus, Bacteroides and Lactobacillus and elevated the levels of indole-3-lactic acid and indole-3-propionic acid. These results demonstrated that astaxanthin regulates tryptophan metabolism by modifying gut microbiota and increasing the levels of indole metabolites, such as indole-3-lactic acid and indole-3-propionic acid. This study provides insights into the physiological activity of astaxanthin and sheds light on the potential for enhancing tryptophan metabolism through dietary manipulation of the gut microbiota.
研究领域:
营养学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Shijing Dong,Liping Guo,Chenyang Xuan,Chenhui Zhu,Zongze Han,Nian Chen,Xinyu Wang,Meng Shen,Xiaoxuan Wei,Hui Yang,Xue Zhang,Man Liu,Simin Zhou,Lu Zhou
Lactobacillus plantarum (L. plantarum ) has shown protective effects in various liver diseases, yet its therapeutic potential and mechanisms in intrahepatic cholestasis remain unelucidated. This study aimed to investigate the therapeutic efficacy and mechanism of L. plantarum in intrahepatic cholestasis using two well-established mouse models induced by α-naphthylisothiocyanate (ANIT) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). The results indicated that L. plantarum significantly alleviated cholestasis-related hepatic inflammation, ductular proliferation, fibrosis, and improved gut barrier integrity. The 16S rRNA sequencing and untargeted metabolomics analysis revealed that the intestinal abundance of L. plantarum was significantly increased after intervention and showed a positive correlation with the level of indole-3-acetic acid (IAA), a key functional metabolite of tryptophan ( r = 0.712, p = 0.003). The elevated IAA levels were closely associated with the improvement of key liver injury indicators. Exogenous IAA supplementation replicated the hepatoprotective effects of L. plantarum in intrahepatic cholestasis. Transcriptome analysis indicated that IAA mediated these benefits primarily through aryl hydrocarbon receptor (AHR) activation, and AHR inhibition markedly attenuated its protective effects. This study reveals that L. plantarum ameliorates intrahepatic cholestasis by enhancing tryptophan metabolism to promote IAA production, which in turn activates the IAA-AHR axis, providing new insights into probiotic and metabolite-based therapies for intrahepatic cholestasis.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）