Neamine(4+)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Neamine(4+)
• 英文别名: [(1S,2R,3R,4S,5R)-5-azaniumyl-2-[(2R,3R,4R,5S,6R)-3-azaniumyl-6-(azaniumylmethyl)-4,5-dihydroxyoxan-2-yl]oxy-3,4-dihydroxycyclohexyl]azanium
• 化学式: C12H30N4O6+4
• 分子量: 326.39
• InChiKey: SYJXFKPQNSDJLI-HKEUSBCWSA-R

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  210
• 氢给体数：
  8
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氧代-戊二酸离子(2-) 、 Neamine(4+) 生成 6'-Oxoparomamine(3+) 、 2-氨基戊二酸酯
  参考文献：
  名称：

  精制新霉素和布丁酶的生物合成中的新胺环。

  摘要：

  在链霉菌NCIMB 8233的新霉素基因簇（neo）中编码的蛋白Neo-11和Neo-18分别被表征为氨基葡萄糖氨基-6'-氧化酶和6'-氨基葡萄糖氨基氨基甲酸酯：L-谷氨酸氨基转移酶。Neo-11和Neo-18的联合活性通过FAD依赖的脱氢机理，然后由吡ido醛5'-磷酸介导的转氨作用，导致新霉素生物合成途径中的巴胺转化为神经胺。Neo-18还显示出在新霉素的C-6'催化脱氨作用，因此表明这两种酶在新霉素的两个新胺环的形成中均具有双功能作用。btrB基因的产物是圆形芽孢杆菌丁酸生物合成基因簇（btr）中neo-18的同源物，其活性与Neo-18相同。

  DOI：

  10.1002/cbic.200600371

文献信息

• The Last Step of Kanamycin Biosynthesis: Unique Deamination Reaction Catalyzed by the α-Ketoglutarate-Dependent Nonheme Iron Dioxygenase KanJ and the NADPH-Dependent Reductase KanK
  作者：Hilda Sucipto、Fumitaka Kudo、Tadashi Eguchi

  DOI：10.1002/anie.201108122

  日期：2012.4.2

  solved: Using heterologous expression, the activities of two enzymes exclusively belonging to the kanamycin biosynthetic pathway have been identified in vitro. A distinctive reaction mechanism (see scheme) to produce kanamycin is proposed and the previously unknown catalytic deamination activity of KanJ dioxygenase is uncovered.

  悬而未决的谜团：使用异源表达，已在体外鉴定了仅属于卡那霉素生物合成途径的两种酶的活性。提出了产生卡那霉素的独特反应机理（参见方案），并且未发现KanJ双加氧酶的先前未知的催化脱氨活性。
• Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation
  作者：Je Won Park、Sung Ryeol Park、Keshav Kumar Nepal、Ah Reum Han、Yeon Hee Ban、Young Ji Yoo、Eun Ji Kim、Eui Min Kim、Dooil Kim、Jae Kyung Sohng、Yeo Joon Yoon

  DOI：10.1038/nchembio.671

  日期：2011.11

  transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non–aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase

  卡那霉素是应用最广泛的抗生素之一，但其生物合成途径仍不清楚。目前的提议表明，卡那霉素生物合成产物通过单一酶促转化呈线性相关。为了探索这个系统，我们通过在不产生氨基糖苷的委内瑞拉链霉菌中异源表达来自卡那霉素链霉菌的假定生物合成基因组合，重建了整个生物合成途径. 出乎意料的是，我们发现生物合成途径包含一个早期分支点，受糖基转移酶的底物混杂控制，导致形成两条平行途径，其中早期中间体被进一步修饰。糖基转移酶交换可以改变通过这两条平行途径的通量，添加其他生物合成酶可用于合成已知的和新的高活性抗生素。这些结果完成了我们对卡那霉素生物合成的理解，并证明了通路工程在体内直接生产临床有用的抗生素和更强大的氨基糖苷类的潜力。
• The oxidoreductases LivQ and NeoQ are responsible for the different 6′-modifications in the aminoglycosides lividomycin and neomycin
  作者：D. Clausnitzer、W. Piepersberg、U.F. Wehmeier

  DOI：10.1111/j.1365-2672.2011.05082.x

  日期：2011.9

  Aims: The 2‐deoxystreptamine‐containing aminoglycoside antibiotics (AGAs) constitute the largest subgroup of the aminoglycosides. Neomycin (NEO) and lividomycin (LIV) are both representatives of the pseudo‐tetrasaccharide group among the NEO‐type AGAs. While NEO contains a 6′‐NH2 group, the 6′‐position remains unmodified in LIV. The aim of the study was to characterize the substrate specificities of the enzymes involved in the C‐6′‐ and C‐6‴‐modification in order to explain the different amination patterns.Methods and Results: We overproduced and purified the enzymes NeoQ (bifunctional 6′‐ and 6‴‐oxidoreductase) and NeoB (bifunctional 6′‐ and‐6‴‐aminotransferase), which had been analysed before (Huang et al. 2007), and compared the enzymatic properties with the corresponding enzymes LivQ (postulated 6‴‐oxidoreductase, 72% identity to NeoQ) and LivB (postulated 6‴‐aminotransferase, 71% identity to NeoB) from the LIV pathway. By applying a newly established photometric assay, we proved that LivQ oxidized only pseudotetrasaccharidic substrates at the 6‴‐position. In contrast, NeoQ accepted also the pseudodisaccharidic paromamine as a substrate and oxidized the 6′‐ and 6‴‐positions on two different precursors of NEO. The aminotransferases LivB and NeoB both transfer NH2 groups to the 6′‐position in the precursor 6′‐oxo‐paromamine and to the 6‴‐position of 6‴‐oxo‐neomycin C.Conclusions: The difference in the modification pattern of NEO and LIV at their 6′‐positions is based only on the difference in the substrate specificities of the oxidoreductases LivQ and NeoQ, respectively. The aminotransferases LivB and NeoB share identical biochemical properties, and both are capable to transaminate the 6′ and also the 6‴‐position of the tested AGAs.Significance and Impact of the Study: Our data provide information to understand the structural variations in aminoglycosides and may be helpful to interpret variations in other natural product bisoynthesis pathways.

  目的：含 2-脱氧链霉胺的氨基糖苷类抗生素（AGAs）是氨基糖苷类药物中最大的亚类。新霉素（NEO）和红霉素（LIV）都是 NEO 型 AGAs 中假四糖类的代表。NEO 含有一个 6′-NH2 基团，而 LIV 的 6′ 位则未被修饰。研究的目的是确定参与 C-6′- 和 C-6‴ 改性的酶的底物特异性，以解释不同的胺化模式：我们过量生产并纯化了 NEOQ（双功能 6′-和 6‴-氧化还原酶）和 NEOB（双功能 6′-和 6‴-氨基转移酶），这两种酶之前已经进行过分析（Huang et al.2007），并将其酶特性与 LIV 途径中的相应酶 LivQ（推测为 6‴-氧化还原酶，与 NEOQ 的同一性为 72%）和 LivB（推测为 6‴-氨基转移酶，与 NEOB 的同一性为 71%）进行了比较。通过应用一种新建立的光度测定法，我们证明 LivQ 只氧化 6‴ 位的伪四糖底物。与此相反，NEOQ 也接受假双糖对氨基的底物，并氧化两种不同的 NEO 前体上的 6′-和 6‴-位点。氨基转移酶 LivB 和 NEOB 都将 NH2 基团转移到前体 6′-oxo-paromamine 的 6′ 位和 6‴-oxo-nEOmycin C 的 6‴ 位：NEO和LIV在其6′位上的修饰模式差异仅基于氧化还原酶LivQ和NEOQ的底物特异性不同。氨基转移酶 LivB 和 NEOB 具有相同的生化特性，它们都能对被测 AGA 的 6′和 6‴ 位进行转氨基：我们的数据为了解氨基糖苷类化合物的结构变化提供了信息，并可能有助于解释其他天然产物双合成途径的变化。
• Unique O-ribosylation in the biosynthesis of butirosin
  作者：Fumitaka Kudo、Takuya Fujii、Shunsuke Kinoshita、Tadashi Eguchi

  DOI：10.1016/j.bmc.2007.04.040

  日期：2007.7

  Using a comparative genetics approach, one or more of the BtrA, BtrL, BtrP, and BtrV proteins encoded in the butirosin biosynthetic gene cluster (btr) from Bacillus circulans SANK72073 were identified as being responsible for an O-ribosylation process leading to the formation of ribostamycin, a key intermediate in this, and related antibiotic biosynthetic pathways. Functional analysis of the recombinantly expressed proteins revealed that both BtrL and BtrP were responsible for the ribosylation of neamine, using 5-phosphoribosyl-l-diphosphate (PRPP) as the ribosyl donor. Further detailed analysis indicated that this process occurs via two discrete steps: with BtrL first catalyzing the phosphoribosylaion of neamine to form 5"-phosphoribostamycin, followed by a BtrP-catalyzed dephosphorylation to generate ribostamycin. To the best of our knowledge, this is the first time that the functional characterization of a glycosyltransferase from an aminoglycoside biosynthetic gene cluster has been reported. (c) 2007 Elsevier Ltd. All rights reserved.
• Enzymatic activity of a glycosyltransferase KanM2 encoded in the kanamycin biosynthetic gene cluster
  作者：Fumitaka Kudo、Hilda Sucipto、Tadashi Eguchi

  DOI：10.1038/ja.2009.107

  日期：2009.12