Asukamycin
(Synonyms: AM1042, Asukamycin A) 目录号 : GC42863
An antitumor antibiotic
Cas No.:61116-33-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Asukamycin is polyketide isolated from the S. nodosus subspecies asukaensis that demonstrates a broad range of antibiotic functions. It has been shown to inhibit growth of various tumor cell lines (IC50s = 1-5 µM) by activating caspases 8 and 3.
| Cas No. | 61116-33-4 | SDF | |
| 别名 | AM1042, Asukamycin A | ||
| Canonical SMILES | O=C1[C@@H]2[C@@H](O2)[C@@](/C=C/C=C/C=C/C(NC3=C(O)CCC3=O)=O)(O)C=C1NC(/C=C/C=C/C=C/C4CCCCC4)=O | ||
| 分子式 | C31H34N2O7 | 分子量 | 546.6 |
| 溶解度 | DMF: Soluble,DMSO: Soluble,Ethanol: Soluble,Methanol: Soluble | 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 | 1.8295 mL | 9.1475 mL | 18.2949 mL |
| 5 mM | 0.3659 mL | 1.8295 mL | 3.659 mL |
| 10 mM | 0.1829 mL | 0.9147 mL | 1.8295 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。
A Pair of Atypical KAS III Homologues with Initiation and Elongation Functions Program the Polyketide Biosynthesis in Asukamycin
Angew Chem Int Ed Engl 2022 May 2;61(19):e202200879.PMID:35218125DOI:10.1002/anie.202200879.
β-Ketoacyl-ACP synthase III (KAS III) is a class of important C-C bond-forming enzymes that mostly catalyze the initiation of polyketide and fatty acid biosynthesis. In this study, we elucidated an unusual polyketide synthase (PKS) system that involves two unique KAS IIIs (AsuC3 and C4) in the biosynthesis of the upper triene chain of Asukamycin. Significantly, AsuC3 and C4 have both initiation and iterative elongation activity, while being functionally biased toward the elongation and initiation steps, respectively. Mutational analysis revealed that their catalytic activities rely on the catalytic triad Cys-His-Asn. Unlike other KAS IIIs, AsuC3 and C4 are very promiscuous and can accept various lengths of acyl-CoAs with either cyclic, branched or linear acyl moieties. By cooperation with the permissive ketoreductase (AsuC7) and dehydratase (AsuC8/C9), a large variety of polyenes can be efficiently synthesized. This study significantly broadens the understanding of KAS IIIs and polyketide biosynthesis.
Biochemical and genetic insights into Asukamycin biosynthesis
J Biol Chem 2010 Aug 6;285(32):24915-24.PMID:20522559DOI:10.1074/jbc.M110.128850.
Asukamycin, a member of the manumycin family metabolites, is an antimicrobial and potential antitumor agent isolated from Streptomyces nodosus subsp. asukaensis. The entire Asukamycin biosynthetic gene cluster was cloned, assembled, and expressed heterologously in Streptomyces lividans. Bioinformatic analysis and mutagenesis studies elucidated the biosynthetic pathway at the genetic and biochemical level. Four gene sets, asuA-D, govern the formation and assembly of the Asukamycin building blocks: a 3-amino-4-hydroxybenzoic acid core component, a cyclohexane ring, two triene polyketide chains, and a 2-amino-3-hydroxycyclopent-2-enone moiety to form the intermediate protoasukamycin. AsuE1 and AsuE2 catalyze the conversion of protoasukamycin to 4-hydroxyprotoasukamycin, which is epoxidized at C5-C6 by AsuE3 to the final product, Asukamycin. Branched acyl CoA starter units, derived from Val, Leu, and Ile, can be incorporated by the actions of the polyketide synthase III (KSIII) AsuC3/C4 as well as the cellular fatty acid synthase FabH to produce the Asukamycin congeners A2-A7. In addition, the type II thioesterase AsuC15 limits the cellular level of omega-cyclohexyl fatty acids and likely maintains homeostasis of the cellular membrane.
Transcriptional regulation and increased production of Asukamycin in engineered Streptomyces nodosus subsp. asukaensis strains
Appl Microbiol Biotechnol 2012 Oct;96(2):451-60.PMID:22555913DOI:10.1007/s00253-012-4084-2.
Asukamycin, a member of the manumycin family of antibiotics, exhibits strong antibacterial, antifungal, and antineoplastic activities. However, its production in the wild-type strain of Streptomyces nodosus subsp. asukaensis ATCC 29757 is relatively low. Recently, the biosynthetic gene cluster for Asukamycin was identified in the producing organism, and among the 36 genes reported in the cluster, six (asuR1-asuR6) were proposed to encode proteins that function as transcriptional regulators. In order to investigate their involvement in Asukamycin biosynthesis and to engineer mutant strains of S. nodosus that are able to produce large amounts of Asukamycin, we carried out in vivo gene inactivation, transcriptional analysis of the biosynthetic genes in the mutants, and gene duplication in the producing strain of S. nodosus. The results show that two of the putative regulatory genes (asuR1 and asuR5) are critical for Asukamycin biosynthesis, whereas others regulate the pathway at various levels. Overexpression of a gene cassette harboring asuR1, asuR2, asuR3, and asuR4 in S. nodosus resulted in changes in morphology of the producing strain and an approximately 14-fold increase of Asukamycin production. However, overexpression of the individual genes did not give a comparable cumulative level of Asukamycin production, suggesting that some, if not all, of the gene products act synergistically to regulate the biosynthesis of this antibiotic.
Antitumor activity of Asukamycin, a secondary metabolite from the actinomycete bacterium Streptomyces nodosus subspecies asukaensis
Int J Mol Med 2009 Nov;24(5):711-5.PMID:19787206DOI:10.3892/ijmm_00000283.
Asukamycin, a manumycin-type metabolite, was isolated by a rapid and easily scalable purification scheme. Thus far, studies on the biological activity of Asukamycin have been limited to its role as an antibacterial and antifungal agent. By using five different tumor cell lines we demonstrate antineoplastic activity of Asukamycin. It inhibited cell growth at concentrations similar to other members of the manumycin family (IC50 1-5 microM). Cytotoxicity of Asukamycin was accompanied by activation of caspases 8 and 3 and was diminished by SB 202190, a specific p38 mitogen-activated protein kinase (MAPK) inhibitor. These data, in combination with earlier observations showing its low in vivo toxicity, indicate that further studies on the potential antitumor activity of Asukamycin are warranted.
A new antibiotic,, Asukamycin, produced by Streptomyces
J Antibiot (Tokyo) 1976 Sep;29(9):876-81.PMID:993129DOI:10.7164/antibiotics.29.876.
Asukamycin, a new antibiotic, has been isolated from the culture broth of a streptomycete designated as Streptomyces nodosus subsp. asukaensis. The antibiotic inhibits the growth of Gram-positive bacteria including Nocardia asteroides. The empirical formula of antibiotic Asukamycin has been proposed as C29H22N2O9 (M.W. 542). An acute toxicity of the antibiotic in mice is LD50 48.5 mg/kg by intraperitoneal injection and it has no effect on mice when it was administered by 450 mg/kg per os.