Neoantimycin
(Synonyms: 新抗霉素) 目录号 : GC44362
An antibiotic
Cas No.:22862-63-1
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
Neoantimycin is an antibiotic originally isolated from S. orinoci that has slight antifungal activity. It is structurally similar to antimycin despite being produced by an unrelated species of Streptomyces. The biosynthetic pathway of neoantimycin has been determined and active analogs discovered.
| Cas No. | 22862-63-1 | SDF | |
| 别名 | 新抗霉素 | ||
| Canonical SMILES | O=C([C@@](C(C)C)([H])OC([C@@H](NC(C1=C(O)C(NC=O)=CC=C1)=O)[C@@H](C)O2)=O)O[C@H](CC3=CC=CC=C3)[C@H](O)C(C)(C)C(O[C@]([C@@H](C)CC)([H])C2=O)=O | ||
| 分子式 | C36H46N2O12 | 分子量 | 698.8 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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 | 1.431 mL | 7.1551 mL | 14.3102 mL |
| 5 mM | 0.2862 mL | 1.431 mL | 2.862 mL |
| 10 mM | 0.1431 mL | 0.7155 mL | 1.431 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。
Biosynthesis of the 15-Membered Ring Depsipeptide Neoantimycin
ACS Chem Biol 2018 May 18;13(5):1398-1406.PMID:29693372DOI:10.1021/acschembio.8b00298.
Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. Of particular interest are the ring-expanded antimycins that show promising anticancer potential and whose biosynthesis remains uncharacterized. Specifically, Neoantimycin and its analogs have been shown to be effective regulators of the oncogenic proteins GRP78/BiP and K-Ras. The Neoantimycin structural skeleton is built on a 15-membered tetralactone ring containing one methyl, one hydroxy, one benzyl, and three alkyl moieties, as well as an amide linkage to a conserved 3-formamidosalicylic acid moiety. Although the biosynthetic gene cluster for neoantimycins was recently identified, the enzymatic logic that governs the synthesis of neoantimycins has not yet been revealed. In this work, the Neoantimycin gene cluster is identified, and an updated sequence and annotation is provided delineating a nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) hybrid scaffold. Using cosmid expression and CRISPR/Cas-based genome editing, several heterologous expression strains for Neoantimycin production are constructed in two separate Streptomyces species. A combination of in vivo and in vitro analysis is further used to completely characterize the biosynthesis of neoantimycins including the megasynthases and trans-acting domains. This work establishes a set of highly tractable hosts for producing and engineering neoantimycins and their C11 oxidized analogs, paving the way for neoantimycin-based drug discovery and development.
Total synthesis of isoneoantimycin
Org Biomol Chem 2023 Mar 15;21(11):2398-2404.PMID:36857695DOI:10.1039/d3ob00099k.
Antimycins are one of the well-known antifungal metabolites produced by Streptomyces bacteria. Neoantimycin and its analogues, the ring-expanded antimycins featuring a 15-membered tetraester ring, have been shown to be effective regulators of the oncogenic proteins GRP78/BiP and K-Ras. Isoneoantimycin was isolated from Streptomyces fradiae IFO12773 (ISP 5063) as a minor metabolite during the fermentation of Neoantimycin and is the first reported antibiotic of the antimycin family without the macrolide core. In this study, we explored the total synthesis and stereochemical assignment of isoneoantimycin as an approach to perform structure-activity studies on neoantimycins. Taking the Neoantimycin biosynthesis pathway into account, we presumed that the stereochemistry of isoneoantimycin is the same as that of Neoantimycin. The synthesis of our target molecule with the (1S,2R,5S,6S,14R,15R,17S) configuration has been achieved by using chiral-pool building blocks. A comparison of the spectroscopic data between the synthetic and natural samples verified our presumption of the stereochemistry of natural isoneoantimycin.
Neoantimycin F, a Streptomyces-Derived Natural Product Induces Mitochondria-Related Apoptotic Death in Human Non-Small Cell Lung Cancer Cells
Front Pharmacol 2019 Sep 18;10:1042.PMID:31619992DOI:10.3389/fphar.2019.01042.
Streptomyces-derived natural products have been become a major focus of anti-tumor drug discovery studies. Neoantimycin F (NAT-F), was isolated from Streptomyces conglobatus by our group. Here, we examined the anti-cancer activities and its underlying molecular mechanisms implicated in NAT-F-induced apoptosis of non-small cell lung cancer (NSCLC) cells. Our results showed that NAT-F exerted excellent growth-inhibitory activity against PC9 and H1299 cells in a concentration-dependent manner. NAT-F-induced cell cycle arrest at S and G0/G1 phase in PC9 and H1299 cells, respectively. Further investigation revealed that the key proteins (including cyclinD1, cyclinE1, cyclinB1, CDK2, and CDK4) were involved in the cell regulation by NAT-F. Additionally, NAT-F significantly increased the production of reactive oxygen species (ROS), induced DNA damage, nuclear condensation, and cell apoptosis in both cell lines. Moreover, loss of the mitochondrial membrane potential (MMP) was markedly induced by NAT-F. Additional results revealed that NAT-F could up-regulate pro-apoptotic protein Bax and down-regulate anti-apoptotic protein Bcl-2, Mcl-1, and Bcl-xL, resulting in cytochrome c release from mitochondria and sequential activation of caspase-9 and -3, as well as the cleavage of poly (ADP-ribose) polymerase. Meanwhile, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK) signaling pathway were also involved in anti-cancer activity of NAT-F in NSCLC cells. Taken together, these findings indicated that NAT-F possessed anti-proliferative effect and induced apoptosis in NSCLC cells in vitro and may be conducive to promote the development of novel anti-NSCLC agents.
Chemical variation from the Neoantimycin depsipeptide assembly line
Bioorg Med Chem Lett 2013 Sep 15;23(18):5123-7.PMID:23932359DOI:10.1016/j.bmcl.2013.07.031.
Here we report the biosynthetic pathway for the Neoantimycin and present three novel Neoantimycin analogues, Neoantimycin D (1), E (2) and F (3), from this assembly system from Streptoverticillium orinoci. Identification of these novel Neoantimycin variants was achieved by selective MS/MS interrogation of natural product extracts using diagnostic fragments of the known neoantimycins. Their structures, including the absolute configurations, were elucidated using a combination of NMR experiments, detailed MS/MS experiments and the advanced Marfey's method. The biosynthetic pathway of Neoantimycin was dissected by genome sequencing data analysis for the first time, which includes a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) assembly lines.
Nuclear magnetic resonance and biosynthetic studies of Neoantimycin and structure elucidation of isoneoantimycin, a minor metabolite related to Neoantimycin
J Nat Prod 1998 Aug;61(8):978-81.PMID:9722479DOI:10.1021/np9800194.
In preparation for biosynthetic studies on the 3,4-dihydroxy-2, 6-dimethyl-5-phenylvaleric acid portion of Neoantimycin (1), the 1H and 13C NMR signals of 1 were assigned unambiguously by means of 2D correlation spectroscopy and NOE experiments. The previously undetermined absolute stereochemistry at C-15 and C-16 was deduced as (S) and (S). The structure of isoneoantimycin (2) was also elucidated. The methyl groups of methionine and propionate were incorporated stereospecifically into C-13 and C-12 of 1, respectively, and the configuration of the methyl group of methionine is inverted in the process. The results also suggest the intervention of phenylpyruvate as an actual precursor.