Increasing the Production of Nattokinase and Vitamin K2 in Natto with Dipicolinic Acid

Sumi, Hiroyuki; Ikeda, Shiori; Ohsugi, Tadanori

doi:10.2174/1874256400903010010

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…This means that someone who eats nattō ingests this amount of dipicolinic acid on a daily basis [13] . Dipicolinic acid is a kind of chelate substance with some notable characteristics such as promoting the growth of B. subtilis natto and increasing the amounts of nattokinase and vitamin K 2 [14,15] . Hagiwara et al [16] reported that sitosterol and fucosterol work on bovine vascular endothelial cells to help release tPA.…”

Section: Discussionmentioning

confidence: 99%

Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells

Yatagai¹,

Maruyama²,

Kawahara³

et al. 2007

Pathophysiol Haemos Thromb

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When heated to a temperature of 70°C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121°C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration.

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Section: Discussionmentioning

confidence: 99%

Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells

Yatagai¹,

Maruyama²,

Kawahara³

et al. 2007

Pathophysiol Haemos Thromb

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“…Many different medium components could affect the synthesis of MK-7. These include carbon source, nitrogen source, phosphate source, surfactants, and activators [9,13,[16][17][18]. In preliminary experiments, the medium constituents were optimized by the onefactor-at-a-time (OFAT) method.…”

Section: Experimental Designmentioning

confidence: 99%

Statistical Optimization of Medium Components by Response Surface Methodology to Enhance Menaquinone-7 (Vitamin K2) Production by Bacillus subtilis

Ahn

2018

Journal of Microbiology and Biotechnology

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Optimization of the culture medium to maximize menaquinone-7 (MK-7) production by Bacillus subtilis strain KCTC 12392BP in static culture was carried out using statistical experimental methods, including one factor at a time, fractional factorial design, and response surface methodology (RSM). Maltose (carbon source), tryptone (nitrogen source), and glycerol (activator) were identified as the key medium components for MK-7 synthesis by the fractional factorial design, and were selected for statistical optimization by RSM. The statistical analysis indicated that, in the range that was studied, maltose, tryptone, and glycerol were all critical factors having profound effects on the production of MK-7, with their coefficients for linear and quadratic all significant at the p < 0.05 level. The established model was efficient and feasible, with a determination coefficient (R 2 ) of 0.9419. The predicted concentrations of maltose, tryptone, and glycerol in the optimal medium were determined as 36.78, 62.76, and 58.90 g/l, respectively. In this optimized medium, the maximum yield of MK-7 reached a remarkably high level of 71.95 ± 1.00 µg/ml after 9 days of static fermentation, which further verified the practicability of this optimized strategy.

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“…After 84 hours of fermentation, they achieved a yield of 5.3 g/kg for iturin A and 51.3 g/kg for poly-γglutamic acid.Xu et al(Xu et al 2020) engineered metabolic pathways and optimized conditions to attain an iturin A yield of 2013.43 ± 32.86 mg/L. Hiroyuki Sumi(Sumi et al 2009) introduced dipicolinic acid for co-fermentation, resulting in maximum nattokinase activity at 479 mm 2 /mL with 16 mM dipicolinic acid and a vitamin K2 yield of 3.26 ± 0.09 µg/mL with 10 mM dipicolinic acid in shake ask fermentation. Wang et al(H Wang et al 2018…”

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Simultaneous Production of Vitamin K2 and Iturin A by Bacillus velezensis ND

Shen,

Cao,

Tang

et al. 2023

Preprint

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Bacillus velezensis is known to produce a diverse array of secondary metabolites, including the ability to synthesize lipopeptides such as iturin A, and additionally produce higher amounts of vitamin K2. Consequently, we sought to employ co-production fermentation to simultaneously generate vitamin K2 and iturin A. In order to significantly reduce fermentation costs and enhance substrate utilization efficiency, this article initially established a straightforward and effective product extraction method that enables the separate collection of vitamin K2 and iturin A from the fermentation broth. Simultaneously, the impacts of glycerol, soybean meal powder, yeast extract powder, and L-glutamic acid sodium, employed as carbon and nitrogen sources in the culture medium, on the co-production of vitamin K2 and iturin A were refined by optimizing factors such as culture temperature, initial pH and the concentrations of trace elements Na+ and K+, as well as additional additives L-glutamic acid sodium. It was discerned that glycerol, soybean meal powder, yeast extract powder, and L-glutamic acid sodium significantly influenced the concurrent production of vitamin K2 and iturin A. As a result, a novel process for the efficient co-production fermentation of vitamin K2 and iturin A was established, thereby enhancing the value-added aspect of the fermentation process. Furthermore, the implementation of a two-compartment biofilm reactor synergistically elevated the co-production efficiency. The yields of vitamin K2 and iturin A reached 46.88 mg/L and 5.58 g/L, respectively. This study provides a theoretical framework and practical implications for the integrated double-product fermentation process.

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Increasing the Production of Nattokinase and Vitamin K2 in Natto with Dipicolinic Acid

Cited by 4 publications

References 11 publications

Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells

Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells

Statistical Optimization of Medium Components by Response Surface Methodology to Enhance Menaquinone-7 (Vitamin K2) Production by Bacillus subtilis

Simultaneous Production of Vitamin K2 and Iturin A by Bacillus velezensis ND

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