(S)-2-methyl butyrate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-2-methyl butyrate
• 英文别名: (S)-alpha-methylbutyrate；(2S)-2-methylbutanoate
• 化学式: C₅H₉O₂
• 分子量: 101.125
• InChiKey: WLAMNBDJUVNPJU-BYPYZUCNSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  40.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-methyl butyrate 在 盐酸 、 MGSNIDAAVAADPVVLMETAFRKAVESSQIPGAVLMARDASGRLNYTRCFGARTVRRDENNQLPPLQVDTPCRLASATKLLTTIMALQCMERGLVRLDETVDRLLPDLCAMPVLEGFDDAGNPRLRERRGKITLRHLLTHTSGLSYVFLHPLLREYVAQGHLQGAEKFGIQNRFAPPLVNDPGAEWIYGAGIDWAGKLVERATGLDLEQYLQENICAPLGITDMTFKLQQRPDMLARRADMTHRNSSDGKLRYDDTVYFRHDGEECFGGQGVFSSPGSYMKVLHSLLKRDGLLLQPGTVDLMFQPALEPRLEEQMNQHMDASPHINYGGPMPMVMRRSFGLGGIIALEDLDGENWRRKGSMTFGGGPNIIWQIDPKAGLCTLVFFQLEPWSDPVCRDLTRTFEKAIYAQYQQG 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 magnesium chloride 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 24.17h， 生成 lovastatin
  参考文献：
  名称：

  Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues

  摘要：

  摘要 本研究通过实验室进化的酰基转移酶 LovD9 对单加林 J 酸的酰化作用，确定了制造他汀类似物的新酰基供体。乙烯基酯和对硝基苯酯已成为 LovD9 催化酰化反应的替代底物。乙烯基酯的产物产率可与α-二甲基丁酰基-S-甲基-3-巯基丙酸酯（DMB-SMMP）（LovD9催化的硫酯）的产物产率一样高，而对硝基苯酯在第一个酰化步骤中的反应活性甚至高于DMB-SMMP，但酰化产物产率却较低。通过量子力学（QM）计算阐明了反应机理。

  DOI：

  10.1002/chem.202300911
• 作为产物：
  描述：

  水 、 美伐他汀 生成 (S)-2-methyl butyrate 、 (4R,6R)-6-[2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-六氢-8-羟基-2-甲基-1-萘基]乙基]四氢-4-羟基-2H-吡喃-2-酮 、 氢(+1)阳离子
  参考文献：
  名称：

  Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus

  摘要：

  Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.

  DOI：

  10.1016/j.ymben.2017.06.005

文献信息

• Structural insights into the catalytic mechanism of lovastatin hydrolase
  作者：Yajing Liang、Xuefeng Lu

  DOI：10.1074/jbc.ra119.011936

  日期：2020.1.24

  The lovastatin hydrolase PcEST from the fungus Penicillium chrysogenum exhibits enormous potential for industrial-scale applications in single-step production of monacolin J, the key precursor for synthesis of the cholesterol-lowering drug simvastatin. This enzyme specifically and efficiently catalyzes the conversion of lovastatin to monacolin J but cannot hydrolyze simvastatin. Understanding the catalytic

  产自青霉青霉的洛伐他汀水解酶PcEST在一步合成莫纳可林J的工业规模应用中显示出巨大的工业潜力，莫纳可林J是合成降胆固醇药物辛伐他汀的关键前体。该酶特异性和有效地催化洛伐他汀向莫纳可林J的转化，但不能水解辛伐他汀。因此，了解PcEST的催化机理和结构-功能关系对于进一步的洛伐他汀水解酶的筛选，工程和商业应用非常重要。在这里，我们解决了四个X射线晶体结构，包括apo PcEST（2.3Å），与莫纳可林J复合的PcEST（2.48Å），与底物类似物辛伐他汀（2.4Å）复合的PcEST，以及灭活的PcEST变体（S57A）洛伐他汀底物（2.3Å）。基于结构的生化分析和诱变分析表明，Ser57（亲核试剂）-Tyr170（通用碱基）-Lys60（通用酸）催化三联体，活性位点周围的氢键网络（Trp344和Tyr127）以及特定的底物结合通道共同决定了PcEST的有效和特异性洛伐他汀水解作用。此外，由辛
• Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus
  作者：Xuenian Huang、Yajing Liang、Yong Yang、Xuefeng Lu

  DOI：10.1016/j.ymben.2017.06.005

  日期：2017.7

  Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
• Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues
  作者：Guillermo García‐Marquina、Reyes Núñez‐Franco、Daniel Grajales‐Hernández、Gonzalo Jiménez‐Osés、Fernando López‐Gallego

  DOI：10.1002/chem.202300911

  日期：2023.7.26

  This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p‐nitrophenyl esters have emerged as alternate substrates for LovD9‐catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α‐dimethyl butyryl‐S‐methyl‐3‐mercaptopropionate (DMB‐SMMP), the thioester for which LovD9 was evolved, p‐nitrophenyl esters display a reactivity even higher than DMB‐SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations.

  摘要 本研究通过实验室进化的酰基转移酶 LovD9 对单加林 J 酸的酰化作用，确定了制造他汀类似物的新酰基供体。乙烯基酯和对硝基苯酯已成为 LovD9 催化酰化反应的替代底物。乙烯基酯的产物产率可与α-二甲基丁酰基-S-甲基-3-巯基丙酸酯（DMB-SMMP）（LovD9催化的硫酯）的产物产率一样高，而对硝基苯酯在第一个酰化步骤中的反应活性甚至高于DMB-SMMP，但酰化产物产率却较低。通过量子力学（QM）计算阐明了反应机理。