16β-hydroxynorethisterone

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 16β-hydroxynorethisterone
• 英文别名: 16β-OH-NET
• 化学式: C₂₀H₂₆O₃
• 分子量: 314.425
• InChiKey: MEYYZWJHHPXXDE-JZEPMIPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  23.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  3.0

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  炔诺酮	norethisterone	68-22-4	C20H26O2	298.425

反应信息

• 作为产物：
  描述：

  炔诺酮 在 氧气 作用下， 以 二甲基亚砜 为溶剂， 反应 8.5h， 生成 16β-hydroxynorethisterone 、 15β-hydroxynorethisterone
  参考文献：
  名称：

  Selective whole-cell biosynthesis of the designer drug metabolites 15- or 16-betahydroxynorethisterone by engineered Cytochrome P450 BM3 mutants

  摘要：

  In the present study, the whole-cell biotransformation using strains expressing CYP BM3 mutants has been evaluated for the stereoselective hydroxylation of the steroid norethisterone (NET), a widely used contraceptive. First, an in vitro CYP BM3 mutant library screen was performed to identify mutants with high activity, as well asstereoselectivity. Subsequently, two different whole-cell setups (resting and growing cells) were tested in two different host organisms (Escherichia coli and Saccharomyces cerevisiae) expressing CYP BM3. It was found that resting E. coli whole cells produced the highest amounts of products and therefore this biocatalytic setup was further optimized for application in a laboratory-scale fermentor. In the optimized fermentor setup, high product yields (0.3 g/L 15 beta-OH-NET and 0.16 g/L 16 beta-OH-NET) were achieved while it was also shown that the regio- and stereoselectivities of the steroid hydroxylations, as determined during the in vitro library screen, were preserved lathe whole-cell system. The combination of a mutant CYP BM3 library and the optimized whole-cell oxidation system represents a promising and cost-effective alternative to a wide range of in vitro biosynthetic routes. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2015.08.003

文献信息

• Selective whole-cell biosynthesis of the designer drug metabolites 15- or 16-betahydroxynorethisterone by engineered Cytochrome P450 BM3 mutants
  作者：Jelle Reinen、Galvin Vredenburg、Karoline Klaering、Nico P.E. Vermeulen、Jan N.M. Commandeur、Maarten Honing、J. Chris Vos

  DOI：10.1016/j.molcatb.2015.08.003

  日期：2015.11

  In the present study, the whole-cell biotransformation using strains expressing CYP BM3 mutants has been evaluated for the stereoselective hydroxylation of the steroid norethisterone (NET), a widely used contraceptive. First, an in vitro CYP BM3 mutant library screen was performed to identify mutants with high activity, as well asstereoselectivity. Subsequently, two different whole-cell setups (resting and growing cells) were tested in two different host organisms (Escherichia coli and Saccharomyces cerevisiae) expressing CYP BM3. It was found that resting E. coli whole cells produced the highest amounts of products and therefore this biocatalytic setup was further optimized for application in a laboratory-scale fermentor. In the optimized fermentor setup, high product yields (0.3 g/L 15 beta-OH-NET and 0.16 g/L 16 beta-OH-NET) were achieved while it was also shown that the regio- and stereoselectivities of the steroid hydroxylations, as determined during the in vitro library screen, were preserved lathe whole-cell system. The combination of a mutant CYP BM3 library and the optimized whole-cell oxidation system represents a promising and cost-effective alternative to a wide range of in vitro biosynthetic routes. (C) 2015 Elsevier B.V. All rights reserved.