fumonisin B1 | 1217458-62-2

• 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
• 英文名称: fumonisin B1
• 英文别名: fumonisin B₁；FB₁；Macrofusine；2-[2-[19-amino-6-(3,4-dicarboxybutanoyloxy)-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid
• CAS: 1217458-62-2；116355-83-0
• 化学式: C₃₄H₅₉NO₁₅
• 分子量: 721.84
• InChiKey: UVBUBMSSQKOIBE-UHFFFAOYSA-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
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，也未有已知的危险反应。

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 Fusarium moniliforme 和其他 F. 属真菌产生。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粒腐烂时，玉米中会显著积累。人类暴露：没有与这种化合物相关的急性毒性的确认记录。现有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尚不明确。动物/植物研究：在所有测试的动物物种中，伏马毒素B1对小鼠、大鼠、马科动物、猪、兔子和非人灵长类动物都具有肝脏毒性。除了叙利亚仓鼠，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。伏马毒素在大鼠、羊、小鼠和兔子中对肾脏有毒。在大鼠和兔子中，肾脏毒性发生在比肝脏毒性更低的剂量下。伏马毒素已知会导致马脑白质软化和猪肺水肿综合征。在某一品系的大鼠中，伏马毒素B1对雄性大鼠具有肝脏致癌性，在另一品系中具有肾脏致癌性。伏马毒素B1是 de novo 神经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）中导致自由神经酰胺碱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性DNA合成，但在低浓度下诱导了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，当口服给药时，这种化合物吸收不良，并且它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。少量在尿液中排出，有些残留在肝脏和肾脏中。

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

• 毒性总结

烟曲霉毒素的结构与鞘磷脂的长链碱基骨架相似，因此能够通过抑制神经酰胺合成酶来阻碍鞘氨醇和更复杂鞘磷脂的生物合成。这导致鞘氨醇、鞘氨醇和可能的鞘氨醇1-磷酸在细胞和组织中的积累，从而引发细胞凋亡。霉菌毒素通常能够通过人类的有机阴离子转运体（hOATs）和有机阳离子转运体（hOCTs）进入肝脏和肾脏。它们还能抑制这些转运体对阴离子和阳离子的摄取，干扰内源代谢物、药物和包括它们自己在内的外源性化合物的分泌。这导致细胞内毒性化合物的积累增加，引起肾脏和肝脏毒性。（A704, L1937, A2947, A3014）

Fumonisins are similar in structure to the long-chain base backbones of sphingolipids, allowing it to inhibit of the biosynthesis of sphingosine and more complex sphingolipids by inhibiting the enzyme ceramide synthase. This causes the accumulation of sphinganine, sphingosine, and possibly also sphingosine 1-phosphate in cells and tissues, leading to apoptosis. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (A704, L1937, A2947, A3014)

来源:Toxin and Toxin Target Database (T3DB)

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)

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，通过灌胃给予相似剂量的 FB1，在尿液中仅回收了 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，通过静脉注射或灌胃的方式给予狒狒（Cercopithecus aethiops）。通过静脉注射给两只雌性狒狒的FB1迅速从血浆中消除，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及其水解类似物形式回收。两只雌性狒狒通过一次灌胃给予14C标记的FB1。在随后的3天内，粪便中放射性物质的排泄平均占给药剂量的61%，尿液排泄占1.2%。从骨骼肌（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，而肠道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、肠道内容和尿液的 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）粪便中伏马毒素B1（FB1）的方法已经开发出来。动物被给予14C标记的FB1，通过用0.1 M乙二胺四乙酸重复提取，回收粪便中的放射性化合物。提取物在反相色谱（C18）固相萃取柱上进行净化，FB1通过o-苯甲醛衍生化和反相高效液相色谱法测定。粪便提取物中FB1的测定方法具有可重复性[相对标准偏差（RSD）为2.6%]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，表明提取的放射性物质主要对应于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，这个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毫克的FB1注射到3个乳腺的灌注血液中，并在150分钟内测定乳液和灌注血清中的水平。FB1通过了乳腺屏障进入乳汁，但浓度如此之低，对消费者来说风险微不足道。

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：
  F,Xn
• 安全说明：
  S16,S26,S36/37
• 危险类别码：
  R11,R20/21/22,R36
• WGK Germany：
  2

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：

  fumonisin B1 在 吡啶 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 28.0h， 生成 N-acetyl-tri-O-acetylfumonisin B₁
  参考文献：
  名称：

  结合伏马毒素B1：通过液相色谱-电喷雾电离串联质谱法分析伏马毒素B1糖和氨基酸缀合物。

  摘要：

  为了研究伏马菌素伪影的形成以及伏马菌素与热处理食品中基质成分（例如糖和蛋白质）的结合，进行了模型实验。将伏马菌素B（1）和水解伏马菌素B（1）与α-d-葡萄糖和蔗糖（单糖和二糖模型），甲基α-d-葡萄糖吡喃糖苷（淀粉模型）以及氨基酸衍生物N-一起孵育α-乙酰基-1-赖氨酸甲酯和BOC-1-半胱氨酸甲酯（蛋白质模型）。通过液相色谱-电喷雾电离-串联质谱法分析形成的反应产物。d-葡萄糖与伏马菌素B（1）或水解伏马菌素B（1）的孵育导致Amadori重排产物的形成。蔗糖，甲基α-d-吡喃葡萄糖苷反应后发现了缀合物，以及带有伏马菌素B（1）的氨基酸衍生物，经水解伏马菌素B（1）加热均未产生任何假象。为了进行结构确定，将甲基α-d-吡喃葡萄糖苷（作为淀粉模型）与伏马菌素B（1）加热形成的稳定反应产物进行纯化，并通过核磁共振波谱鉴定为伏马菌素三碳烯酸侧链与甲基的二酯。 α-d-吡喃葡萄糖苷。这些模型实

  DOI：

  10.1021/jf0344338

文献信息

• Use of liquid chromatography-high-resolution mass spectrometry for isolation and characterization of hydrolyzed fumonisins and relevant analysis in maize-based products
  作者：Annalisa De Girolamo、Veronica M. T. Lattanzio、Roberto Schena、Angelo Visconti、Michelangelo Pascale

  DOI：10.1002/jms.3342

  日期：2014.4

  and FB2), from 10 to 210 microg/kg for partially hydrolyzed fumonisins (sum of PHFB1 and PHFB2) and from 30 to 200 microg/kg for hydrolyzed fumonisins (sum of HFB1 and HFB2). This is the first report of the isolation of PHFB2 and the co-occurrence of FB1, FB2, PHFB1, PHFB2, HFB1 and HFB2 in maize products. Considering the growing use of nixtamalized and maize-based products, the monitoring of fumonisins

  报道了通过化学水解纯伏马菌素（FB1和FB2）合成部分水解的伏马菌素（PHFB1和PHFB2）和水解的伏马菌素（HFB1和HFB2）以及通过液相色谱-高分辨率质谱法（LC- HRMS）。确定了部分水解形式的FB1和FB2的两个结构异构体，即PHFB（1a）和PHFB（1b）以及PHFB（2a）和PHFB（2b）。PHFB1的反应产率为21％（两个异构体之和），HFB1的反应产率为52％，PHFB2（两个异构体的总数）为31％，HFB2的反应产率为30％。每种分离的化合物的纯度均> 98％。同时测定伏马菌素及其部分和全部水解衍生物的LC-HRMS方法应用于24种玉米和玉米基产品的自然污染样品。大多数样品（24个样品中的18个）被伏马菌素B1和B2污染。伏马菌素与部分水解的伏马菌素和水解的伏马菌素同时存在于四个尼克坦化样品中（三个麻辣粉和一个玉米饼片）。在一个玉米粒样本和四个玉米基产品样本（即
• Determination of the mycotoxin fumonisin B1 and identification of its partially hydrolysed metabolites in the faeces of non-human primates
  作者：G.S. Shephard、P.G. Thiel、E.W. Sydenham、R. Vleggaar、J.F. Alberts

  DOI：10.1016/0278-6915(84)90032-2

  日期：1994.1

  A method has been developed for the determination of fumonisin B1 (FB1) in the faeces 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

  已经开发出一种测定非人类灵长类动物（黑长尾猴）粪便中的伏马菌素B1（FB1）的方法。给动物施用14 C标记的FB1，并通过用0.1 M乙二胺四乙酸反复萃取来回收粪便中的放射性化合物。将萃取物在反相（C18）固相萃取柱上进行净化，然后通过邻苯二甲醛衍生化和反相HPLC测定FB1。测定粪便提取物中FB1的分析方法可重复[2.6％相对标准偏差（RSD）]和准确的（从加标的空白提取物中回收率93 +/- 2.9％RSD）。使用HPLC和薄层色谱法对粪便中FB1的鉴定进行了确认，结果表明提取的放射性主要对应于FB1和一种新的代谢产物，其色谱性质与霉菌毒素相似。通过质谱和核磁共振波谱鉴定出新的代谢产物是部分水解的FB1的两个结构异构体的平衡混合物，它们是通过霉菌毒素的一个酯基的水解而形成的。
• 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。