Study of Antibacterial Substances Found in Natto

吡啶二羧酸的分析用Janssen等的比色法测定了纳豆菌中DPA（2，6-吡啶二甲酸）的含量，结果表明，DPA的最大含量约占菌体总干重的2.4-3.6%，并比较了DPA及其衍生物喹啉酸的抑菌活性（2，3-吡啶二甲酸）、2，4-吡啶二甲酸、异吲哚乙酸（2，5-吡啶二甲酸）和3，5-吡啶二甲酸-揭示了这种抗菌活性是DPA所独有的。此外，研究了各种金属离子对抗菌活性的影响，结果表明，添加Ca^++>、Fe^++>、Co^++>和Zn^++>（均为二价离子）强烈抑制了抗菌活性，还表明添加DPA增加了纳豆枯草芽孢杆菌产生纳豆激酶的量。在Miyagino型、目黑型、高桥型和成濑型四种纳豆枯草芽孢杆菌中， ...更多信息 增加了纳豆激酶的产生量。例如，在Miyagino型的情况下，纤维蛋白平板的纤维蛋白溶解活性是未添加DPA的样品的两倍，在37℃下4小时后为256.1 mm^2/30 μl（纳豆激酶活性为1，500 FU/ml）。加入10种烟酸有关物质的对比试验表明，吡啶二甲酸的作用最强，终浓度为5×10 ~（-1）<-3>mol/l的DPA可显著抑制人三磷酸腺苷（ATP）引起的血小板聚集反应，以及凝血酶将纤维蛋白原转化为纤维蛋白的反应。很明显，在5×10^mol/l浓度下，如血栓弹性描记术中所观察到的那样，完全抑制了凝血反应，而在DPA衍生物的情况下，即使在10 mM浓度下也没有观察到这种强烈的作用。人凝血酶原时间、活性区域的凝血活酶时间或优球蛋白溶解时间没有变化。尽管在30 μM二磷酸腺苷（ADP）的情况下观察到人血液中的血小板聚集<-3>，很明显，当存在5×10^ M DPA时，这种聚集发生剂量依赖性抑制<-3>。计算出的CI为<50>1.8×10^ M的相当低的浓度<-3>，并且远强<-2>于临床使用中加入阿司匹林的情况（4.0×10^ M）。少

An analysis of dipicolinic acid (DPA,2,6-pyridinedicarboxylic acid) contained in Bacillus subtilis natto cells using the colorimetric method of Janssen and others showed that the largest DPA content is approximately 2.4-3.6% of the total dry weight.A comparison of the antibacterial activity of DPA and its derivatives-quinolic acid (2,3-pyridine dicarboxylic acid), 2,4-pyridine dicarboxylic acid, isoinchlorendic acid (2,5-pyridine dicarboxylic acid), and 3,5-pyridine dicarboxylic acid-revealed that this antibacterial activity is unique to DPA. Moreover, an investigation into the effects of various metal ions on the antibacterial activity showed that the activity is strongly inhibited through the addition of Ca^<++>,Fe^<++>,Co^<++>, and Zn^<++>, all divalent ions.It was also shown that the addition of DPA increases the amount of nattokinase produced by Bacillus subtilis natto. In four types of Bacillus subtilis natto, the Miyagino, Meguro, Takahashi and Naruse types, DPA with a 2 mM conc … More entration increased the amount of nattokinase produced. In the case of the Miyagino type, for example, the fibrinolytic activity for fibrin plates was double the level seen for the sample with no DPA added, at 256.1 mm^2/30 μl at 37℃ after four hours (1,500 FU/ml for the nattokinase activity). A comparison test, with 10 types of nicotinic acid-related substances added, showed that dipicolinic acid had the strongest effect.DPA with a final concentration of 5×10^<-3> mol/l was found to substantially inhibit the platelet aggregation reaction caused by human adenosine triphosphate(ATP), as well as the reaction of thrombin converting fibrinogen into fibrin. It became clear that at 5×10^<-3> mol/l, there was a complete inhibition of the blood coagulation reaction as observed in thromboelastography, while such strong effects were not observed in the case of DPA derivatives, even at 10 mM. There were no changes in human prothrombin time, the thromboplastin time for the active areas, or euglobulin lysis time.Although platelet aggregation in human blood is observed with 30 μM of adenosine diphosphate(ADP), it became clear that dose-dependent inhibition of this aggregation occurs when there is 5×10^<-3> M of DPA. The calculated CI_<50> was at the fairly low concentration of 1.8×10^<-3> M, and far stronger (4.0×10^<-2> M) than in the case of adding aspirin for clinical use. Less