O-乙酰基-l-丝氨酸 | 5147-00-2

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 天然氨基酸及其衍生物
• 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: O-乙酰基-l-丝氨酸
• 中文别名: O-乙醯絲胺酸
• 英文名称: O-acetyl-L-serine
• 英文别名: O-acetylserine；(2S)-3-acetyloxy-2-azaniumylpropanoate
• CAS: 5147-00-2
• 化学式: C₅H₉NO₄
• mdl: MFCD00037771
• 分子量: 147.131
• InChiKey: VZXPDPZARILFQX-BYPYZUCNSA-N

物化性质

• 熔点：
  151.5-151.8 °C
• 沸点：
  297.7±35.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)
• 溶解度：
  酸水溶液（少量，超声处理）、甲醇（非常少量）、水（少量溶解）
• 物理描述：
  Solid
• 碰撞截面：
  130.5 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2922509090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  -20°C

制备方法与用途

生物活性

O-Acetylserine 是细菌和植物中半胱氨酸生物合成的中间物。

靶点

Human 内源性代谢物

体外研究

O-乙酰丝氨酸（OAS）是硫同化过程中的中心代谢物，为半胱氨酸的合成提供碳骨架。通过硫酸盐还原产生的硫化物会被整合到 OAS 中形成半胱氨酸。OAS 具有信号传导功能，在植物的硫状况不受影响的情况下也能导致特定基因集转录水平的变化。外源施加 OAS 会增加硫酸盐转运体和腺苷 5′-磷酸硫酸还原酶基因的表达，这与 OAS 转录诱导模型一致。

反应信息

• 作为反应物：
  描述：

  O-乙酰基-l-丝氨酸 在 2-吗啉乙磺酸 、 N-terminal decahistidine-tagged Salmonella typhimurium O-acetylserine sulfhydrylase-A Q142A mutant pyridoxal 5'-phosphate internal Schiff base ketoenamine tautomer 、 水 、 还原型辅酶Ⅰ 、 L-lactate dehydrogenase 作用下， 生成 piruvate
  参考文献：
  名称：

  Identification of the Structural Determinants for the Stability of Substrate and Aminoacrylate External Schiff Bases in O-Acetylserine Sulfhydrylase-A

  摘要：

  O-Acetylserine sulfhydrylase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the final step in the cysteine biosynthetic pathway in enteric bacteria and plants, the replacement of the beta-acetoxy group of O-acetyl-L-serine (OAS) by a thiol to give L-cysteine. Previous studies of the K41A mutant enzyme showed L-methionine bound in an external Schiff base (ESB) linkage to PLP as the enzyme was isolated. The mutant enzyme exists in a closed form, optimizing the orientation of the cofactor PLP and properly positioning active site functional groups for reaction. The trigger for closing the active site upon formation of the ESB is thought to be interaction of the substrate alpha-carboxylate with the substrate-binding loop comprised of T68, S69, G70, and N71, and Q142, which is positioned above the cofactor as one looks into the active site. To probe the contribution of these residues to the active site closing and orientation of PLP in the ESB, T68, S69, N71, and Q142 were changed to alanine. Absorbance, fluorescence, near UV-visible CD, and P-31 NMR spectral studies and pre-steady state kinetic studies were used to characterize the mutant enzymes. All of the mutations affect closure of the active site, but to differing extents. In addition, the site appears to be more hydrophilic given that the ESBs do not exhibit a significant amount of the enolimine tautomer. No buildup of the alpha-aminoacrylate intermediate (AA) is observed for the T68A and Q142A mutant enzymes. However, pyruvate is produced at a rate much greater than that of the wild-type enzyme. Data suggest that T68 and Q142 play a role in stabilizing the AA. Both residues donate a hydrogen bond to one of the carboxylate oxygens of the methionine ESB and may also be responsible for the proper orientation of the ESB to generate the AA. The S69A and N71A mutants exhibit formation of the AA, but the rate constant for its formation from the ESB is decreased by 1 order of magnitude compared to that of the wild type. S69 donates a hydrogen bond to the substrate carboxylate in the ESB, while N71 donates hydrogen bonds to O3' of the cofactor and the carboxylate of the ESB; these side chains may also affect the orientation of the ESB. Data suggest that interaction of intermediates with the substrate-binding loop and Q142 gives a properly aligned Michaelis complex and facilitates the beta-elimination reaction.

  DOI：

  10.1021/bi100473v
• 作为产物：
  描述：

  L-丝氨酸 、 乙酰氯 在 盐酸 、 溶剂黄146 作用下， 反应 30.0h， 以75%的产率得到O-乙酰基-l-丝氨酸
  参考文献：
  名称：

  三氯环氧乙烷与蛋白质和dna的反应：加合物的不稳定性和功能的调节。

  摘要：

  三氯乙烯（TCE）显示出几种类型的毒性，其中某些可能是生物活化的结果。P450氧化可生成亲电子的TCE氧化物。我们先前分析了由三氯乙烯氧化物与蛋白质反应形成的N（6）-酰基赖氨酸加合物[Cai，H.和Guengerich，FP（2000）Chem。Res。毒药。13，327-335]；但是，在长时间的蛋白水解和衍生化条件下，我们无法测量酯加合物。在TCE氧化物与模型多肽胰岛素和促肾上腺皮质激素（ACTH，残基1-24）反应期间，通过质谱直接观察到蛋白质氨基酸加合物。大部分（80％）的蛋白质加合物在生理条件下均不稳定，并且总体t（1/2）约为1小时，这表明它们是由Cys反应形成的酯型加合物，Ser，Tyr或Thr残基以及在TCE氧化物水解中形成的中间体。合成的O-乙酰基-L-Ser和O-乙酰基-L-Tyr在pH 8.0下的半衰期分别为1 h和10 min，这与蛋白质加合物的稳定性相似。用五种

  DOI：

  10.1021/tx000185n

文献信息

• Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols
  作者：Yong Wang、Xiaoxu Chen、Wenkang Cai、Linzhi Tan、Yutong Yu、Boyang Han、Yuxuan Li、Yuanzhe Xie、Yeyu Su、Xiaozhou Luo、Tao Liu

  DOI：10.1002/anie.202014540

  日期：2021.4.26

  accessible aromatic thiols. We demonstrate that nearly 50 ncAAs with a diverse array of structures can be biosynthesized from these simple small‐molecule precursors by hijacking the cysteine biosynthetic enzymes, and the resulting ncAAs can subsequently be incorporated into proteins via an expanded genetic code. Moreover, we demonstrate that bioorthogonal reactive groups such as aromatic azides and

  将结构新颖的非规范氨基酸 (ncAAs) 结合到蛋白质中对于科学和生物医学应用都很有价值。为了扩大可用 ncAAs 的结构多样性并减轻化学合成它们的负担，我们开发了一种通用且简单的生物合成方法，通过用经济的市售或合成可获得的芳香硫醇喂养细胞，将新型 ncAAs 基因编码为重组蛋白。我们证明，通过劫持半胱氨酸生物合成酶，可以从这些简单的小分子前体生物合成近 50 种具有多种结构的 ncAAs，随后可以通过扩展的遗传密码将生成的 ncAAs 整合到蛋白质中。而且，
• In Situ Deprotection and Incorporation of Unnatural Amino Acids during Cell-Free Protein Synthesis
  作者：Isaac N. Arthur、James E. Hennessy、Dharshana Padmakshan、Dannon J. Stigers、Stéphanie Lesturgez、Samuel A. Fraser、Mantas Liutkus、Gottfried Otting、John G. Oakeshott、Christopher J. Easton

  DOI：10.1002/chem.201203923

  日期：2013.5.17

  (DE3) used for cell‐free protein synthesis removes a wide range of α‐amino acid protecting groups by cleaving α‐carboxyl hydrazides; methyl, benzyl, tert‐butyl, and adamantyl esters; tert‐butyl and adamantyl carboxamides; α‐amino form‐, acet‐, trifluoroacet‐, and benzamides; and side‐chain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions

  大肠杆菌BL21 Star（DE3）的S30提取物可用于无细胞蛋白质合成，可通过裂解α-羧基酰肼去除大量的α-氨基酸保护基团。甲基，苄基，叔丁基和金刚烷基酯; 叔丁基和金刚烷酰胺; α-氨基甲酰胺，乙酰胺，三氟乙酰胺和苯甲酰胺; 以及侧链酰肼和酯。在标准条件下产生游离氨基酸并将其掺入蛋白质中。该方法允许在原位进行氨基酸的脱保护以避免单独的加工步骤。这种方法的优势通过有效结合化学难治性（S）-4-氟亮氨酸（S）-4,5-脱氢亮氨酸和（2 S，3 R）-4-氯缬氨酸通过直接使用它们各自的前体即（S）-4-氟亮氨酸酰肼（S）-4,5转变成蛋白质脱氢亮氨酸酰肼和（2 S，3 R）-4-氯缬氨酸甲酯。这些结果还表明，氟，脱氢亮氨酸和氯缬氨酸通过正常的生物合成机制被掺入蛋白质中，分别代替亮氨酸和异亮氨酸。
• Facile Synthesis of <i>S</i> -Substituted L-Cysteines with Nano-sized Immobilized <i>O</i> -Acetylserine Sulfhydrylase
  作者：Akbar K. Vahidi、Zunsheng Wang、Zhi Li

  DOI：10.1002/cctc.201800577

  日期：2018.9.7

  Many S‐substituted l‐cysteines are useful pharmaceutical intermediates but require a simple synthesis method. Here we developed enzymatic synthesis of several S‐aryl‐l‐cysteines and S‐benzyl‐l‐cysteine directly from O‐acetylserine (OAS) with immobilized O‐acetylserine sulfhydrylase CysM. Novel iron‐oxide magnetic nanoparticles (MNPs) with cobalt‐nitrilotriacetic acid function were prepared with a diameter

  许多小号取代升-cysteines是有用的医药中间体，但需要一个简单的合成方法。在这里，我们开发了几个酶促合成小号-芳基-升-cysteines和小号苄基升从半胱氨酸直接ø -acetylserine（OAS）用固定化ö-乙酰丝氨酸巯基化酶CysM。制备具有钴-三氮三乙酸功能的新型氧化铁磁性纳米颗粒（MNP），其直径为80 nm，产率为75％。通过亲和力附着将无细胞提取物中His标记的CysM直接固定在MNP上，提供了稳定的纳米生物催化剂，具有97％的酶负载效率和93％的游离酶活性。固定化酶催化苄硫醇和OAS的生物转化，以88％的收率得到S-苄基-1-半胱氨酸。纳米生物催化剂还显示出高可回收性，在第五个循环中保留了95％的生产率。固定化的CysM接受各种芳基硫醇与OAS反应，从而产生了一些由S取代的l半胱氨酸的产率为60–96％。
• Biosynthesis of β-(1,2,4-triazol-1-yl)alanine in higher plants
  作者：Fumio Ikegami、Yumiko Komada、Masuko Kobori、Douglas R. Hawkins、Isamu Murakoshi

  DOI：10.1016/0031-9422(90)85176-g

  日期：1990.1

  4-triazol-1-yl)Alanine, an important metabolite of the triazole-based fungicide Myclobutanil, was shown to be derived from O-acetyl- l -serine and 1,2,4-triazole by cysteine synthase in higher plants. Some properties of this enzyme in the biosynthesis of β-(1,2,4-triazol-1-yl)alanine are described.

  摘要 β-(1,2,4-triazol-1-yl)丙氨酸是三唑类杀菌剂 Myclobutanil 的一种重要代谢物，被证明来源于 O-乙酰-l-丝氨酸和 1,2,4-三唑通过高等植物中的半胱氨酸合酶。描述了这种酶在 β-(1,2,4-triazol-1-yl) 丙氨酸生物合成中的一些特性。
• Establishment of an <i>In Vitro</i> <scp>d</scp> -Cycloserine-Synthesizing System by Using <i>O</i> -Ureido- <scp>l</scp> -Serine Synthase and <scp>d</scp> -Cycloserine Synthetase Found in the Biosynthetic Pathway
  作者：Narutoshi Uda、Yasuyuki Matoba、Takanori Kumagai、Kosuke Oda、Masafumi Noda、Masanori Sugiyama

  DOI：10.1128/aac.02291-12

  日期：2013.6

  We have recently cloned a DNA fragment containing a gene cluster that is responsible for the biosynthesis of an antituberculosis antibiotic, d -cycloserine. The gene cluster is composed of 10 open reading frames, designated dcsA to dcsJ . Judging from the sequence similarity between each putative gene product and known proteins, DcsC, which displays high homology to diaminopimelate epimerase, may catalyze the racemization of O -ureidoserine. DcsD is similar to O -acetylserine sulfhydrylase, which generates l -cysteine using O -acetyl- l -serine with sulfide, and therefore, DcsD may be a synthase to generate O -ureido- l -serine using O -acetyl- l -serine and hydroxyurea. DcsG, which exhibits similarity to a family of enzymes with an ATP-grasp fold, may be an ATP-dependent synthetase converting O -ureido- d -serine into d -cycloserine. In the present study, to characterize the enzymatic functions of DcsC, DcsD, and DcsG, each protein was overexpressed in Escherichia coli and purified to near homogeneity. The biochemical function of each of the reactions catalyzed by these three proteins was verified by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and, in some cases, mass spectrometry. The results from this study demonstrate that by using a mixture of the three purified enzymes and the two commercially available substrates O -acetyl- l -serine and hydroxyurea, synthesis of d -cycloserine was successfully attained. These in vitro studies yield the conclusion that DcsD and DcsG are necessary for the syntheses of O -ureido- l -serine and d -cycloserine, respectively. DcsD was also able to catalyze the synthesis of l -cysteine when sulfide was added instead of hydroxyurea. Furthermore, the present study shows that DcsG can also form other cyclic d -amino acid analogs, such as d -homocysteine thiolactone.

  摘要 我们最近克隆了一个 DNA 片段，其中含有一个负责抗结核抗生素生物合成的基因簇、 d -环丝氨酸。该基因簇由 10 个开放阅读框组成，分别为 dcsA 到 dcsJ .从每个推定基因产物与已知蛋白质之间的序列相似性来看，DcsC 与二氨基亚硒酸酯外延酶同源性很高，可能会催化 Omega 的外消旋化。 O -尿苷酸的外消旋化。DcsD 与 O -乙酰丝氨酸巯基酶相似，后者可生成 l -半胱氨酸。 O -乙酰- l 因此，DcsD 可能是生成 O-乙酰基-l-半胱氨酸的合成酶。 O -脲 l -丝氨酸的合成酶。 O -乙酰-l-丝氨酸 l -丝氨酸和羟基脲。DcsG 与具有 ATP-抓取折叠的酶家族相似，可能是一种 ATP 依赖性合成酶，能将 O-乙酰基-丝氨酸转化为丝氨酸。 O -脲 d -丝氨酸转化为 d -环丝氨酸。在本研究中，为了鉴定 DcsC、DcsD 和 DcsG 的酶功能，将每种蛋白在 大肠杆菌 并纯化至接近均一。通过薄层色谱法（TLC）、高效液相色谱法（HPLC）和质谱法（在某些情况下）验证了这三种蛋白质催化的每个反应的生化功能。这项研究的结果表明，通过使用三种纯化酶和两种市售底物的混合物 O -乙酰- l -丝氨酸和羟基脲，可合成 d -环丝氨酸的合成。这些 体外 这些体外研究得出的结论是，DcsD 和 DcsG 是合成 O-环丝氨酸的必要条件。 O -脲 l -丝氨酸和 d -环丝氨酸。DcsD 还能催化 l -丝氨酸和 d -环丝氨酸的合成。 l 当加入硫化物而不是羟基脲时，DcsD 也能催化合成 l -半胱氨酸。此外，本研究还表明，DcsG 还能形成其他环 d -氨基酸类似物，如 d -高半胱氨酸硫内酯。