Neoaureothin
(Synonyms: NSC 260179, Spectinabilin) 目录号 : GC44363A bacterial metabolite
Cas No.:59795-94-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Neoaureothin is a bacterial metabolite that has been found in Streptomyces. It is an androgen receptor (AR) antagonist that inhibits binding of dihydrotestosterone (DHT) to ARs (IC50 = 13 μM) and inhibits DHT-induced expression of prostate-specific antigen in LNCaP cells (IC50 = 1.75 nM). Neoaureothin is cytotoxic to A549, HCT116, and HepG2 cells (IC50s = 34.3, 47, and 37.2 μg/ml, respectively). It also has nematocidal activity against the pine wood nematode B. xylophilus (LC50 = 0.84 μg/ml) and increases survival of P. densiflora trees inoculated with B. xylophilus.
| Cas No. | 59795-94-7 | SDF | |
| 别名 | NSC 260179, Spectinabilin | ||
| Canonical SMILES | CC(/C=C1CO[C@@H](C(OC(OC)=C2C)=C(C)C2=O)C\1)=C\C(C)=C\C(C)=C\C3=CC=C([N+]([O-])=O)C=C3 | ||
| 分子式 | C28H31NO6 | 分子量 | 477.6 |
| 溶解度 | DMF: soluble,DMSO: soluble,Ethanol: soluble,Methanol: soluble | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0938 mL | 10.469 mL | 20.938 mL |
| 5 mM | 0.4188 mL | 2.0938 mL | 4.1876 mL |
| 10 mM | 0.2094 mL | 1.0469 mL | 2.0938 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Non-colinear polyketide biosynthesis in the aureothin and Neoaureothin pathways: an evolutionary perspective
Chembiochem 2007 Oct 15;8(15):1841-9.PMID:17763486DOI:10.1002/cbic.200700309.
Aureothin and Neoaureothin (spectinabilin) represent rare nitroaryl-substituted polyketide metabolites from Streptomyces thioluteus and Streptomyces orinoci, respectively, which only differ in the lengths of the polyene backbones. Cloning and sequencing of the 39 kb Neoaureothin (nor) biosynthesis gene cluster and its comparison with the aureothin (aur) pathway genes revealed that both polyketide synthase (PKS) assembly lines are remarkably similar. In both cases the module architecture breaks with the principle of colinearity, as individual PKS modules are used in an iterative fashion. Parsimony and neighbour-joining phylogenetic studies provided insights into the evolutionary process that led to the programming of these unusual type I PKS systems and to prediction of which modules act iteratively. The iterative function of the first module in the Neoaureothin pathway, NorA, was confirmed by a successful cross-complementation.
Evolution of metabolic diversity in polyketide-derived pyrones: using the non-colinear aureothin assembly line as a model system
Phytochemistry 2009 Oct-Nov;70(15-16):1833-40.PMID:19651421DOI:10.1016/j.phytochem.2009.05.022.
Polyketide-derived pyrones are structurally diverse secondary metabolites that are represented in all three kingdoms of life and are endowed with various biological functions. The aureothin family of Streptomyces metabolites was chosen as a model to study the factors governing structural diversity and the evolutionary processes involved. This review highlights recent insights into the non-colinear aureothin and Neoaureothin modular type I polyketide synthase (PKS), aromatic starter unit biosynthesis, polyketide tailoring reactions, and a non-enzymatic polyene splicing cascade. Pyrone biosynthesis in bacteria, fungi, and plants is compared. Finally, various strategies to increase metabolic diversity of aureothin derivatives through mutasynthesis, pathway engineering, and biotransformation are presented. The unusual aureothin and Neoaureothin assembly lines thus not only represent a model for PKS evolution, but provided important insights into non-canonical enzymatic processes that could be employed for the production of antitumor and antifungal agents.
Quorum sensing-based metabolic engineering of the precursor supply in Streptomyces coelicolor to improve heterologous production of Neoaureothin
Biotechnol Bioeng 2023 Apr 12.PMID:37042226DOI:10.1002/bit.28400.
Streptomyces are important industrial bacteria that produce pharmaceutically valuable polyketides. However, mass production on an industrial scale is limited by low productivity, which can be overcome through metabolic engineering and the synthetic biology of the host strain. Recently, the introduction of an auto-inducible expression system depending on microbial physiological state has been suggested as an important tool for the industrial-scale production of polyketides. In this study, titer improvement by enhancing the pool of CoA-derived precursors required for polyketide production was driven in a quorum sensing (QS)-dependent manner. A self-sustaining and inducer-independent regulatory system, named the QS-based metabolic engineering of precursor pool (QMP) system, was constructed, wherein the expression of genes involved in precursor biosynthesis was regulated by the QS-responsive promoter, scbAp. The QMP system was applied for Neoaureothin production in a heterologous host, Streptomyces coelicolor M1152, and productivity increased by up to 4-fold. In particular, the engineered hyperproducers produced high levels of Neoaureothin without adversely affecting cell growth. Overall, this study showed that self-regulated metabolic engineering mediated by QS has the potential to engineer strains for polyketide titer improvement.
Emulating evolutionary processes to morph aureothin-type modular polyketide synthases and associated oxygenases
Nat Commun 2019 Sep 2;10(1):3918.PMID:31477708DOI:10.1038/s41467-019-11896-1.
Polyketides produced by modular type I polyketide synthases (PKSs) play eminent roles in the development of medicines. Yet, the production of structural analogs by genetic engineering poses a major challenge. We report an evolution-guided morphing of modular PKSs inspired by recombination processes that lead to structural diversity in nature. By deletion and insertion of PKS modules we interconvert the assembly lines for related antibiotic and antifungal agents, aureothin (aur) and Neoaureothin (nor) (aka spectinabilin), in both directions. Mutational and functional analyses of the polyketide-tailoring cytochrome P450 monooxygenases, and PKS phylogenies give contradictory clues on potential evolutionary scenarios (generalist-to-specialist enzyme evolution vs. most parsimonious ancestor). The KS-AT linker proves to be well suited as fusion site for both excision and insertion of modules, which supports a model for alternative module boundaries in some PKS systems. This study teaches important lessons on the evolution of PKSs, which may guide future engineering approaches.
Freedom and constraint in engineered noncolinear polyketide assembly lines
Chem Biol 2015 Feb 19;22(2):229-40.PMID:25660274DOI:10.1016/j.chembiol.2014.12.014.
Many pharmacologically important natural products are assembled by modular type I polyketide synthases (PKS), which typically act in a unidirectional fashion. The synthases producing the unusual nitro-substituted polyketides Neoaureothin (nor, also called spectinabilin) and aureothin (aur) are exceptional, as they employ individual modules iteratively. Here, we investigate the plasticity of the nor PKS and the factors governing the number of elongations catalyzed by the noncanonical module. Surprisingly, we observe that the nor PKS can mediate an additional chain elongation to yield the higher homolog homoneoaureothin. Furthermore, we design several truncated variants of the nor PKS to use them in the context of artificial assembly lines for aureothin and homoaureothin. The resulting polypropionate derivatives provide valuable insights into chain length control and reveal structure-activity relationships relating to the size of the polypropionate backbones. Overall, we show that iterative modules are remarkably adaptable while downstream modules are gatekeepers that select for correct polyketide chain length.