伏马毒素B1 | 116355-83-0

• 物质功能分类: 分析化学 - 标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 伏马毒素B1
• 中文别名: 伏马菌素B1
• 英文名称: fumonisin B1
• 英文别名: FB1；(2R)-2-[2-[(5R,6R,7S,9S,11R,16R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid
• CAS: 116355-83-0
• 化学式: C₃₄H₅₉NO₁₅
• 分子量: 721.84
• InChiKey: UVBUBMSSQKOIBE-DSLOAKGESA-N

物化性质

• 熔点：
  >60oC
• 沸点：
  713.81°C (rough estimate)
• 密度：
  1.2207 (rough estimate)
• 闪点：
  6 °C
• 溶解度：
  溶于水（高达 25 mg/ml）。
• 颜色/状态：
  Powder
• 碰撞截面：
  258 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  50
• 可旋转键数：
  31
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  289
• 氢给体数：
  8
• 氢受体数：
  16

ADMET

毒理性

• 毒性总结

识别：伏马毒素B1是伏马毒素中最普遍的一种，由真菌串珠镰刀菌和其他镰刀菌属产生。纯净物质是一种白色吸湿性粉末，可溶于水、乙腈-水和甲醇。该物质在食品加工温度和光照下稳定。伏马毒素B1是与玉米相关的最常见的真菌代谢物。当天气条件有利于玉米穗腐时，玉米中会显著积累。人类暴露：没有关于这种化合物与急性毒性有关的确认记录。可用的相关性研究建议饮食暴露与食管癌之间存在关联。其他关于伏马毒素B1潜在致癌性的研究结论不确定。动物/植物研究：伏马毒素B1对所有测试的动物种类（包括小鼠、大鼠、马科动物、猪、兔子和非人灵长类动物）都具有肝毒性。除了叙利亚仓鼠外，只有在母体毒性同时或之后才会观察到胚胎毒性或致畸性。伏马毒素对猪、大鼠、绵羊、小鼠和兔具有肾毒性。在大鼠和兔子中，肾毒性发生在低于肝毒性的剂量下。伏马毒素已知会引起马脑白质病和猪肺水肿综合征。对某一品系的大鼠具有肝致癌性，对另一品系具有肾致癌性。伏马毒素B1是脱氧鞘脂代谢的特异性抑制剂。这种化合物抑制细胞生长，并在动物、植物和一些酵母（如酿酒酵母）中导致自由鞘脂基的积累和脂质代谢的改变。它没有在大肠杆菌中诱导基因突变，也没有在原代大鼠肝细胞中诱导非计划DNA合成，但在低浓度下诱导剂量依赖性的染色体畸变增加。这种化合物对植物有毒，损害细胞膜并减少叶绿素合成。根据使用猪、产蛋鸡和长尾猴的研究，这种化合物口服给药时吸收不良，并迅速从血浆或循环中消除并在粪便中回收；胆汁排泄很重要；在一些动物中，肠肝循环很重要。少量通过尿液排出，有些保留在肝脏和肾脏中。

IDENTIFICATION: Fumonisin B1 is the most prevalent of the fumonisins and produced by the fungus Fusarium moniliforme and other F. species. The pure substance is a white hygroscopic powder and is soluble in water, acetonitrile-water and methanol. The material is stable at food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with maize. Significant accumulation in maize occurs when weather conditions favor kernel rot. HUMAN EXPOSURE: There are no confirmed records of acute toxicity associated with this compound. Available correlation studies suggest a link between dietary exposure and esophageal cancer. Other studies are inconclusive as to the potential carcinogenicity of Fumonisin B1. ANIMAL/PLANT STUDIES: Fumonisin B1 is hepatotoxic in all animal species tested including mice, rats, equids, pigs, rabbits and non-human primates. With the exception of Syrian hamsters, embryotoxicity or teratogenicity is only observed concurrent with or subsequent to maternal toxicity. Fumonisins are nephrotoxic in pigs, rats, sheep, mice and rabbits. In rats and rabbits, renal toxicity occurs at lower doses than hepatotoxicity. The fumonisins are known to cause equine leukoencephalomalacia and porcine pulmonary edema syndrome. It is hepatocarcinogenic to male rats in one strain and nephrocarcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid metabolism. This compound inhibits cell growth and causes accumulation of free sphingoid bases and alteration of lipid metabolism in animals, plants and in some yeasts such as Saccharomyces cerevisae. It did not induce gene mutations in bacteria or unscheduled DNA synthesis in primary rat hepatocytes, but induced a dose dependent increase in chromosomal aberrations at low concentrations. This compound is phytotoxic, damages cell membranes and reduces chlorophyll synthesis. This compound is poorly absorbed when dosed orally based on studies using pigs, laying hens and Vervet monkeys and it is rapidly eliminated from the plasma or circulation and recovered in the feces; biliary excretion is important; enterohepatic cycling is important in some animals. Small amounts are excreted in the urine, and some is retained in the liver and kidney.[

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于人类来说，证据不足以证明由镰刀菌产生的毒素具有致癌性。对于实验动物来说，有足够的证据表明含有大量伏马毒素的镰刀菌培养物具有致癌性。对于实验动物来说，伏马毒素B1的致癌性证据有限。总体评估：由镰刀菌产生的毒素可能对人类具有致癌性（2B组）。/由镰刀菌产生的毒素/

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium moniliforme. There is sufficient evidence in experimental animals for the carcinogenicity of cultures of Fusarium moniliforme that contain significant amounts of fumonisins. There is limited evidence in experimental animals for the carcinogenicity of fumonisin B1. Overall evaluation: Toxins derived from Fusarium moniliforme are possibly carcinogenic to humans (Group 2B). /Toxins derived from Fusarium moniliforme/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：伏马毒素B1

IARC Carcinogenic Agent:Fumonisin B1

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专论：第82卷（2002年）一些传统草药药物，一些霉菌毒素，萘和苯乙烯

IARC Monographs:Volume 82: (2002) Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

Fumonisin B1（FB1）是 Sheldon 镰刀菌产生的镰刀菌素类次级代谢物中的主要化合物，与一些人类和动物疾病有关。在大鼠腹腔注射（7.5 mg/kg）后，FB1 迅速被吸收，并在注射后 20 分钟内达到血浆中的最高浓度。此后，它从血浆中迅速清除，表现出单指数消除阶段，符合一个半衰期为 18 分钟的一室模型。收集 24 小时和 48 小时的尿液样本表明，只有 16% 的给药剂量未发生代谢并以原形在尿液中排出，且全部在给药后第一个 24 小时内排出。与此相反，相同剂量的 FB1 经灌胃给药后，尿液中仅回收了 0.4% 的 FB1。

Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Fumonisin B1 (FB1)，是真菌Fusarium moniliforme Sheldon的一种有毒和致癌的次级代谢产物，可以通过静脉注射或灌胃的方式给予食蟹猴（Cercopithecus aethiops）。通过静脉注射FB1给两只雌性食蟹猴，FB1从血浆中迅速消除，消除阶段的平均半衰期为40分钟。在给药后5天内对尿液和粪便的分析显示，平均47%的剂量以FB1及其水解类似物的形式回收。给两只雌性食蟹猴单次灌胃14C标记的FB1。在随后的3天内，放射性物质通过粪便排出的平均量为给药剂量的61%，通过尿液排出的量为1.2%。在骨骼肌（1%）、肝脏（0.4%）、大脑（0.2%）、肾脏、心脏、血浆、红细胞和胆汁（每个0.1%）中以低水平回收残留放射性物质，而肠内容物占放射性剂量的另外12%。总的来说，76%的给药放射性物质被回收。对粪便、肠内容物和尿液的分析表明，这些样本中超过90%的放射性物质是由FB1及其水解产物引起的。

Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一种用于测定非人灵长类（长尾猴）粪便中伏马菌素B1（FB1）的方法已经开发出来。动物被喂食了标记有14C的FB1，通过用0.1 M乙二胺四乙酸反复提取，回收粪便中的放射性化合物。提取物在反相（C18）固相萃取柱上进行净化，然后通过o-苯基甲醛衍生化和反相高效液相色谱法测定FB1。粪便提取物中FB1的测定方法具有可重复性[2.6%相对标准偏差（RSD）]和准确性（从加标空白提取物中的回收率为93 +/- 2.9% RSD）。通过高效液相色谱和薄层色谱确认了粪便中FB1的鉴定，表明提取的放射性主要对应于FB1和一个具有与霉菌毒素相似色谱性质的新代谢物。通过质谱和核磁共振光谱鉴定出新代谢物是部分水解FB1的两个结构异构体的平衡混合物，这些异构体是通过霉菌毒素的一个酯基的水解形成的。

A method has been developed for the determination of fumonisin B1 (FB1) in the feces of non-human primates (vervet monkeys). The animals were dosed with 14C-labelled FB1, and the radioactive compounds in faeces were recovered by repeated extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned-up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The analytical method for the determination of FB1 in the fecal extracts was reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed that the radioactivity extracted corresponded mainly to FB1 and a new metabolite with chromatographic properties similar to those of the mycotoxin. The new metabolite was identified by mass spectrometry and nuclear magnetic resonance spectroscopy to be an equilibrium mixture of the two structural isomers of partially hydrolysed FB1, which are formed by hydrolysis of one of the ester groups of the mycotoxin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

真菌毒素伏马毒素B1（FB1）会引起动物的各种健康问题，而流行病学证据表明它与人类食管癌有关。我们使用隔离灌注的牛乳腺研究了FB1进入牛乳的情况。将2毫克FB1注入3个乳腺的灌注血液中，并在150分钟内测定了乳汁和灌注血清中的水平。FB1穿过了乳腺屏障进入乳汁，但浓度如此之低，对消费者来说风险可以忽略不计。

The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals, while epidemiological evidence suggests it is linked to human esophageal cancer. We investigated the carry-over of FB1 into bovine milk using the isolated perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3 udders, and milk and perfused serum levels were determined for 150 min. FB1 passed through the mammary barrier into the milk, but in such low concentrations as to present a negligible risk for consumers.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,F,T
• 危险类别码：
  R40
• 危险品运输编号：
  UN 3172
• WGK Germany：
  2,3
• RTECS号：
  TZ8350000
• 海关编码：
  29221990
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 安全说明：
  S16,S36/37

制备方法与用途

背景 伏马毒素（Fumonisin，Macrofusine）主要发生在玉米上，包括至少15种相近的毒素，其中最主要的是伏马毒素B1（Fumonisin B1，FB1）。尽管在150年前就发现伏马毒素对马有影响，正式鉴定还是在20世纪80年代中期。伏马毒素是几种镰刀菌（Fusarium moniliforme）的极性代谢产物，其基本结构是一种包含甲基和氨基的长链羟基烃链。两个羟基被酯化到两个丙-1,2,3-三羧酸上。

生物活性 Fumonisin B1 是一种由 Fusarium moniliforme 产生的霉菌毒素，是 sphingosine N-acyltransferase (ceramide synthase) 的有效抑制剂，破坏鞘脂从头生物合成。Fumonisin B1 是最丰富和最有毒的伏马菌素。

靶点 Sphingosine N-acyltransferase

体外研究 Fumonisin B1 改变了猴肾细胞中的基因表达和信号传导通路，增加了 LLC-PK1 肾细胞中鞘脂代谢的初始破坏以及鞘胺醇的积累。在大鼠星形胶质细胞中引起凋亡类型的 DNA 损伤。

类别 有毒物质

毒性分级 剧毒

急性毒性 口服-猴 TDL0: 1 毫克/公斤

可燃性危险特性 可燃，火场排出辛辣刺激烟雾

储运特性 库房低温、通风、干燥；与食品原料分开存放

灭火剂 水、二氧化碳、干粉、砂土

反应信息

• 作为反应物：
  描述：

  伏马毒素B1 在 硼烷 、 水 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 16.0h， 生成 (R)-5-Hydroxy-3-hydroxymethyl-pentanoic acid (1S,3S,5R,10R,12S,13S)-5,10,12-triacetoxy-13-acetylamino-1-[(1R,2R)-1-((R)-5-hydroxy-3-hydroxymethyl-pentanoyloxy)-2-methyl-hexyl]-3-methyl-tetradecyl ester
  参考文献：
  名称：

  组合的合成/ CD策略的伏马毒素B（1）的三碳烯酸侧链的立体化学分配。

  摘要：

  圆二色性（CD）激子手性方法用于伏马菌素B（1）1a（FB（1））的三碳烯酸（TCA）侧链的立体化学分配。使用2-萘甲酸酯还原的TCA部分发色衍生化，绝对构型显示为R。为进一步确认，与伏马菌素B（1）的TCA基团相关的旋光二羟基叔丁酸酯2作为模型化合物。

  DOI：

  10.1021/jo0000630
• 作为产物：
  描述：

  在 盐酸 、 palladium hydroxide on carbon 、 氢气 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 18.0h， 以45%的产率得到伏马毒素B1
  参考文献：
  名称：

  Pereira, Claney L.; Chen, Yi-Hung; McDonald, Frank E., Journal of the American Chemical Society, 2009, vol. 131, p. 6066 - 6067

  摘要：

  DOI：

文献信息

• The absolute stereochemistry of the ester functions of fumonisin B1
  作者：Oliver E. Edward、Barbara A. Blackwell、Alex B. Driega、Corrine Bensimon、John W. ApSimon

  DOI：10.1016/s0040-4039(99)00824-2

  日期：1999.6

  Synthesis of an optically active γ-lactone related to tricarballylic acid (TCA) and correlation of this to the same lactone derived from the two sidechain TCA esters at C-14 and C-15 of fumonisin B1 has established that these esters have the R configuration.

  合成与三碳烯丙酸（TCA）相关的旋光性γ-内酯，并将其与来自伏马菌素B 1的C-14和C-15上两个侧链TCA酯的相同内酯的相关性已确定这些酯具有R配置。
• Biodegradation of Fumonisins by the Consecutive Action of a Fusion Enzyme
  作者：Kailin Li、Song Yu、Dianzhen Yu、Huikang Lin、Na Liu、Aibo Wu

  DOI：10.3390/toxins14040266

  日期：——

  that FUMDI enzyme and its reaction products had no negative effect on cell viability and did not induce cell apoptosis, oxidative stress, or endoplasmic reticulum (ER) stress in a human gastric epithelial cell line (GES-1). The results indicated that these FBs degradation products cannot have adverse effects in a cell model. In conclusion, a safe and efficient fumonisin-degrading enzyme was discovered

  伏马菌素 (FBs) 是一种有毒的霉菌毒素，通常存在于食品和饲料中。FBs 可以诱发许多方面的毒性，从而对人类和动物健康造成不利影响；因此，有必要研究减少伏马菌素污染的方法。在我们的研究中，我们通过重叠聚合酶链式反应 (PCR)将羧酸酯酶基因 ( fumD ) 和氨基转移酶基因 ( fumI )连接起来，生成了一种称为 FUMDI 的重组融合酶。融合酶FUMDI在宿主毕赤酵母（P. Pastoris ）中成功秘密表达) GS115，并对其表达进行了优化。我们的研究结果表明，融合酶 FUMDI 对伏马菌素 B1 (FB1) 和其他常见的 FBs，如伏马菌素 B2 (FB2) 和伏马菌素 B3 (FB3) 具有较高的生物降解活性，并且在 24 内几乎完全降解每种毒素 5 μg/mL。 H。我们还发现，FUMDI 酶及其反应产物对细胞活力没有负面影响，并且不会在人胃上皮细胞系 (GES-1) 中诱导细胞凋亡、氧化应激或内质网
• ACIDOPHILIC FUSARIUM OXYSPORUM STRAIN, METHODS OF ITS GROWTH AND METHODS OF ITS USE
  申请人：The Fynder Group, Inc.

  公开号：EP3712248A1

  公开（公告）日：2020-09-23

  The present invention provides isolated acidophilic Fusarium oxysporum strain MK7, or a progeny thereof, compositions comprising this strain or a progeny thereof, methods of growing the strain or a progeny thereof, and methods of using the strain or a progeny thereof.

  本发明提供了分离的嗜酸镰孢菌株 MK7 或其后代、包含该菌株或其后代的组合物、培养该菌株或其后代的方法以及使用该菌株或其后代的方法。
• Acidophilic fusarium oxysporum strains, methods of their production and methods of their use
  申请人：Sustainable Bioproducts, Inc.

  公开号：US10344306B2

  公开（公告）日：2019-07-09

  The present invention provides isolated acidophilic Fusarium oxysporum strains, such as MK7, and their progeny, compositions comprising such strains and their progeny, methods of producing such strains and their progeny, and methods of using such strains and their progeny.

  本发明提供了分离的嗜酸镰孢菌株（如 MK7）及其后代、包含这些菌株及其后代的组合物、生产这些菌株及其后代的方法以及使用这些菌株及其后代的方法。
• Filamentous fungal biomats, methods of their production and methods of their use
  申请人：SUSTAINABLE BIOPRODUCTS, INC.

  公开号：US10577579B2

  公开（公告）日：2020-03-03

  A novel method of growing fungi is disclosed which uses an engineered artificial media and produces high density filamentous fungi biomats that can be harvested with a minimum of processing and from which fungal products such as antibiotics, proteins, and lipids can be isolated, the method resulting in lowered fungus cultivation costs for energy usage, oxygenation, water usage and waste stream production.

  本发明公开了一种新颖的真菌生长方法，该方法使用工程化人工培养基，生产出高密度丝状真菌生物垫，只需进行少量处理即可收获，并可从中分离出抗生素、蛋白质和脂质等真菌产品。