抗荚膜菌素 | 28978-07-6

• 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: 抗荚膜菌素
• 英文名称: anticapsin
• 英文别名: L-anticapsin；(2S)-2-azaniumyl-3-[(1R,2S,6R)-5-oxo-7-oxabicyclo[4.1.0]heptan-2-yl]propanoate
• CAS: 28978-07-6
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: KHVZXXWDPSCGEK-MGVQOFIGSA-N

物化性质

• 熔点：
  240 °C (decomp)
• 沸点：
  415.9±30.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  抗荚膜菌素 在 水 作用下， 生成 (S)-β-<(1S,2R,3R)-4,4-dihydroxy-2,3-epoxycyclohex-1-yl>alanine
  参考文献：
  名称：

  立体控制抗衣壳蛋白的对映体特异性合成

  摘要：

  描述了抗衣壳蛋白（3）修饰结构的立体控制对映体特异性合成。还已经观察到抗衣壳素的羰基具有显着的亲电性，显示出很高的水合和烯醇化倾向。提出了在抑制氨基葡萄糖合成酶过程中抗衣壳素水合形式的可能作用。

  DOI：

  10.1016/0040-4020(95)98714-s
• 作为产物：
  描述：

  β-<(1S,4S)-1-(tert-btuyldiphenylsilyloxy)cyclohex2-en-4-yl>-(S)-alanine methyl ester 在 吡啶 、 氟化铵 、 phosphate buffer 、 四丙基高钌酸铵 、 N-甲基吗啉氧化物 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 氯仿 、 乙腈 为溶剂， 反应 54.0h， 生成 抗荚膜菌素
  参考文献：
  名称：

  Stereocontrolled enantiospecific synthesis of anticapsin: revision of the configuration

  摘要：

  通过立体控制的对映选择性合成抗蕈素，可以修改结构3中的C-4构型；此外，抗蕈素的羰基还表现出很强的水合和烯醇化倾向。

  DOI：

  10.1039/c39930001332

文献信息

• Structural and enzymatic characterization of BacD, an<scp>L</scp>-amino acid dipeptide ligase from<i>Bacillus subtilis</i>
  作者：Yasuhito Shomura、Emi Hinokuchi、Hajime Ikeda、Akihiro Senoo、Yuichi Takahashi、Jun-ichi Saito、Hirofumi Komori、Naoki Shibata、Yoshiyuki Yonetani、Yoshiki Higuchi

  DOI：10.1002/pro.2058

  日期：2012.5

  BacD is an ATP‐dependent dipeptide ligase responsible for the biosynthesis of L‐alanyl‐L‐anticapsin, a precursor of an antibiotic produced by Bacillus spp. In contrast to the well‐studied and phylogenetically related D‐alanine: D‐alanine ligase (Ddl), BacD synthesizes dipeptides using L‐amino acids as substrates and has a low substrate specificity in vitro. The enzyme is of great interest because of

  BacD是一种依赖ATP的二肽连接酶，负责L-丙氨酰-L-抗溶衣蛋白酶的生物合成，这是一种由芽孢杆菌属产生的抗生素的前体。与经过深入研究和系统发育相关的D-丙氨酸：D-丙氨酸连接酶（Ddl）相比，BacD使用L-氨基酸作为底物来合成二肽，并且在体外具有较低的底物特异性。该酶备受关注，因为它在工业蛋白质工程中可能用于环境友好地生物学生产有用的肽化合物（例如生理活性肽，人造甜味剂和抗生素），但其底物特异性及其催化机制的决定因素尚无定论。由于缺乏结构信息而尚未建立。在这项研究中，我们报告BACD的晶体结构在复杂与ADP和中间模拟，磷酸化次膦大号-alanyl-大号-苯丙氨酸，精制至2.5Å分辨率。复杂的结构表明，ADP和两个镁离子以类似于Ddl的方式结合。但是，二肽的方向相反，因此，氨基酸结合腔的入口位置不同。对两个突变体Y265F和S185A的酶促表征表明，至少在以L-苯丙氨酸为底物的反应中，
• <i>ywfE</i>in<i>Bacillus subtilis</i>Codes for a Novel Enzyme,<scp>l</scp>-Amino Acid Ligase
  作者：Kazuhiko Tabata、Hajime Ikeda、Shin-ichi Hashimoto

  DOI：10.1128/jb.187.15.5195-5202.2005

  日期：2005.8

  The ATP-dependent carboxylate-amine/thiol ligase superfamily is known to contain enzymes catalyzing the formation of various types of peptide, such as d-alanyl-d-alanine, polyglutamate, and gamma-peptide, but, curiously, no enzyme synthesizing alpha-dipeptides of l-amino acids is known. We attempted to find such an enzyme. By in silico screening based on the consensus sequence of the superfamily followed

  已知ATP依赖的羧酸胺/硫醇连接酶超家族包含催化各种类型的肽（例如d-丙氨酰-d-丙氨酸，聚谷氨酸和γ-肽）形成的酶，但奇怪的是，没有可合成α的酶1-氨基酸的β-二肽是已知的。我们试图找到这种酶。通过基于超家族的共有序列进行计算机筛选，然后使用纯化的酶进行体外测定以避免合成肽的降解，发现枯草芽孢杆菌的ywfE编码形成L-丙氨酰-1的活性-来自谷氨酰胺和谷氨酰胺的谷氨酰胺，ATP水解成ADP。没有形成AMP，支持了该酶属于超家族的观点。出人意料的是，该酶接受了各种各样的1-氨基酸。在测试的231种L-氨基酸组合中，获得了111种组合的反应产物，并通过高效液相色谱分析确定了44种α-二肽，而未检测到三肽或更长的肽，并且d-氨基酸呈惰性。根据这些结果，我们提出ywfE编码超家族的一个新成员，即I-氨基酸连接酶。
• Enantioselective Total Synthesis of the Antifungal Natural Products Chlorotetaine, Bacilysin, and Anticapsin and of Related Compounds: Revision of the Relative Configuration
  作者：Hanno Wild

  DOI：10.1021/jo00089a019

  日期：1994.5

  Enantioselective and diastereoselective syntheses of the title antifungal natural products and some of their diastereoisomers are described. Key steps include the diastereoselective 1,6-addition of bislactim ether 14 and a stereoselective, deprotonation of ketone 17 using lithium (S,S)-bis(1-phenylethyl)amide as a chiral base. All natural products possess the (S)-configuration at C-1 of the substituted cyclohex(en)yl residues of the C-terminal amino acids, which contradicts the assignments in the literature. At physiological pH most of the dipeptides are instable and react by an intramolecular 1,4-addition with the formation of 6-oxoperhydroindoles.
• Action and Timing of BacC and BacD in the Late Stages of Biosynthesis of the Dipeptide Antibiotic Bacilysin
  作者：Jared B. Parker、Christopher T. Walsh

  DOI：10.1021/bi3016229

  日期：2013.2.5

  Biosynthesis of the dipeptide antibiotic bacilysin, encoded by the seven Bacillus subtilis genes bacA-G, involves diversion of flux from prephenate to the noncognate amino acid anticapsin. The anticapsin warhead is then ligated to the C-terminus of L-alanine to produce mature bacilysin. We have previously noted the formation of two diastereomers of tetrahydrotyrosine (4S- and 4R-H(4)Tyr) by tandem action of the four purified enzymes BacABGF. BacC (oxidase) and BacD (ligase) have been hypothesized to be remaining late stage enzymes in bacilysin biosynthesis. Using a combination of BacCD in vitro studies, B. subtilis deletion mutants, and isotopic feeding studies, we were able to determine that the H(4)Tyr diastereomers are actually shunt products that are not on-pathway to bacilysin biosynthesis. Dihydroanticapsin and dihydrobacilysin accumulate in extracts of a Delta bacC strain and are processed to anticapsin and then bacilysin upon addition of BacC and BacD, respectively. These results suggest the epoxide group in bacilysin is installed in an earlier step of bacilysin biosynthesis, while BacC oxidation of the C-7-hydroxyl and the subsequent BacD ligation of anticapsin to L-Ala are the penultimate and ultimate steps of bacilysin biosynthesis, respectively.
• Single Mutation Alters the Substrate Specificity of <scp>l</scp>-Amino Acid Ligase
  作者：Takeo Tsuda、Mana Asami、Yoshiaki Koguchi、Shuichi Kojima

  DOI：10.1021/bi500292b

  日期：2014.4.29

  L-Amino acid ligase (Lal) catalyzes the formation of a dipeptide from two L-amino acids in an ATP-dependent manner and belongs to the ATP-grasp superfamily. Bacillus subtilis YwfE, the first identified Lal, produces the dipeptide antibiotic bacilysin, which consists of L-Ala and L-anticapsin. Its substrate specificity is restricted to smaller amino acids such as L-Ala for the N-terminal end of the dipeptide, whereas a wide range of hydrophobic amino acids including L-Phe and L-Met are recognized for the C-terminal end in vitro. We determined the crystal structures of YwfE with bound ADP-Mg2+-Pi and ADP-Mg2+-L-Ala at 1.9 and 2.0 angstrom resolutions, respectively. On the basis of these structures, we generated point mutants of residues that are considered to participate in the recognition of L-Ala and measured their ATPase activity. The conserved Arg328 is suggested to be a crucial residue for L-Ala recognition and catalysis. The mutation of Trp332 to Ala caused the enzyme to hydrolyze ATP, even in the absence of L-Ala, and the structure of this mutant protein appeared to show a cavity in the N-terminal substrate-binding pocket. These results suggest that Trp332 plays a key role in restricting the substrate specificity to smaller amino acids such as L-Ala. Moreover, Trp332 mutants can alter the substrate specificity and activity depending on the size and shape of substituted amino acids. These observations provide sufficient scope for the rational design of Lal to produce desirable dipeptides. We propose that the positioning of the conserved Arg residue in Lal is important for enantioselective recognition of L-amino acids.