Bioanalysis
·
2024
·
IF 1.9
Xiemin Qi,Ning Chen,Qinxin Song,Yanan Chu,Haiping Wu,Jingwen Shan,Huijie Yue,Guohua Zhou
Aim: Differences are existed in the bioactivity among various vitamin K (VK) forms. To investigate the correlation between clinical parameters of initial anticoagulation and plasma levels of VK1 and VK2 (MK-4 and MK-7), it was necessary to establish a quantitative method for simultaneous determination.Materials & methods: Plasma samples in cardiovascular patients were extracted by cyclohexane and analyzed using a C18 column. Baseline concentrations of VK1, MK-4 and MK-7 were 0.98 ± 0.52 ng/ml, 0.45 ± 0.13 ng/ml and 0.65 ± 0.31 ng/ml, respectively. The concentrations of MK-7 and total VKs were significantly relevant to INR0, respectively (p = 0.010 and p = 0.048, respectively).Conclusion: Thus, when adjusting anticoagulation dosage, concentrations of various VK homologues might be considered.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2024
·
IF 3.7
Xilin Huang,Xuli Gao,Junbao Huang,Yani Luo,Wei Tao,Mingyu Guo,Yongyuan Liu,Jing Wu,Yu Chen,Yan Liu
A recombinant strain (BS168-Δ bdhA ) that increased co-production of MK-7 and NK was constructed by knocking out the 2,3-butanediol dehydrogenase gene ( bdhA ) of Bacillus subtilis 168 to reduce the carbon spillover. The results showed that the 2,3- butanediol content in the recombinant strain was reduced by 64% to 2.76 g/L. The recombinant strain had an MK-7 production of 30.6 mg/L and an NK activity of 6.5 FU/mL. RNA-Seq analysis showed that: bdhA knockdown blocked the carbon flux of 2,3-butanediol and promoted glycerol uptake, and the carbon flux flowed more to the MK-7 and NK synthesis pathways. The negative regulator of NK, codY , was down-regulated by 2.19-fold. secA , which is responsible for the energy supply of transmembrane proteins, was down-regulated by 0.37-fold, the Tat secretion pathway was up-regulated by 2.8-fold and 0.5-fold for tatAD and tatC , respectively. This study revealed the mechanism of co-production of MK-7 and NK in recombinant strains for the first time and revealed potential molecular targets to promote the co-production of MK-7 and NK, which will provide a new strategy for metabolic engineering to increase the production of MK-7 and NK.
研究领域:
微生物学
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分子生物学
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代谢工程
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DOI
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Wei Tao,Xinyu Shan,Said Nawab,Zhangchenyu Ni,Elvis Kwame Adinkra,Mingyu Guo,Yifeng Jiang,Yu Chen,Chuanchao Wu,Yan Liu
Menaquinone-7 (MK-7), a subtype of Vitamin K 2 , is in high demand within the healthcare sector due to its health benefits. This study proposes a two-stage fermentation strategy combining submerged fermentation with leakage fermentation to enhance MK-7 production in a Bacillus subtilis mutant strain and preliminarily reveal its potential metabolic mechanisms. The Results showed that this strategy achieved a total MK-7 yield of 163.56 mg/L, representing an 85.48% increase over conventional biofilm fermentation, among which extracellular MK-7 production was significantly increased by 269.65%. Results from scanning electron microscopy, fluorescence microscopy, and flow cytometry confirmed that the enhanced MK-7 production was closely associated with increased membrane permeability induced by Brij-58. Furthermore, integrating gas chromatography–ion mobility spectrometry (GC-IMS) and untargeted metabolomics analyses revealed that the highly active central carbon metabolism in the first stage promoted cell growth and MK-7 precursor accumulation, while the possible diversion of carbon flux to secondary metabolic pathways in the second stage facilitated efficient MK-7 biosynthesis. Meanwhile, it was found that the increase in membrane permeability might be attributed to oxidative stress induced by Brij-58, thereby facilitating the efflux of intracellular metabolites and effectively alleviating excessive intracellular MK-7 accumulation. These findings could serve as a potential industrial reference for future process optimization and scale-up validation of MK-7 fermentation, while also offering useful insights for addressing yield bottlenecks in other microbial metabolites.
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DOI
高影响因子
Bioresources and Bioprocessing
·
2025
·Vol. 12
·期 1
·1-18
·
IF 5.1
Zhang Rui,Wang Han,Wang Li,Zheng Zhiming
Menaquinone-7, a form of vitamin K 2 , plays a critical role in the treatment of hemorrhagic diseases caused by vitamin K deficiency and in the prevention of bone fractures. Microbial fermentation has emerged as a promising method for MK-7 production due to its high product optical purity and significant physiological activity. However, the current production efficiency of MK-7 remains insufficient to meet industrial demands. In this study, we employed a combination of single-factor experiments, Plackett-Burman design, steepest ascent experiments, and Box-Behnken design to optimize the fermentation medium for MK-7 production by Bacillus subtilis BS - Δ ackA . Through regression analysis and consideration of practical production constraints, the optimal fermentation medium parameters were determined as follows: 20 g/L sucrose, 20.7 g/L glycerol, 47.3 g/L soy peptone, 4 g/L yeast extract, and 1.9 g/L KH 2 PO 4 , 0.1 g/L MgSO 4 ·7 H 2 O. Under these optimized conditions, the MK-7 yield reached 154.6 ± 1.32 mg/L. The experimental results demonstrated excellent stability and reliability, aligning closely with the model predictions. This study significantly enhances MK-7 production at the shake-flask fermentation level, providing valuable insights for large-scale industrial applications.
研究领域:
微生物发酵
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生物技术
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生物工程
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应用微生物学
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营养科学
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PubMed
高影响因子
BRITISH JOURNAL OF NUTRITION
·
2023
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IF 3.6
Fan Du,Min Yan,Lili Duan,Guolong Xie,Xiuhua Yao,Wenjing Hu,Yu Liu,Min Meng,Jiepeng Chen,Di Shao
Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
研究领域:
药理学
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营养学
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临床研究
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分析化学
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DOI
PubMed
高影响因子
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