Althiomycin
(Synonyms: NSC 102809) 目录号 : GC49039
A thiazole antibiotic
Cas No.:12656-40-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Althiomycin is a polyketide synthase-derived thiazole antibiotic originally isolated from S. althioticus.1 It is active against Gram-positive bacteria, including S. aureus, S. epidermidis, and S. pyogenes (MICs = 25, 25, and 3.1 µg/ml, respectively).2 Althiomycin inhibits protein synthesis in E. coli when used at concentrations of 1 and 10 µg/ml but not in isolated rabbit reticulocytes at 100 µg/ml.3
1.Gerc, A.J., Song, L., Challis, G.L., et al.The insect pathogen Serratia marcescens Db10 uses a hybrid non-ribosomal peptide synthetase-polyketide synthase to produce the antibiotic althiomycinPLoS One7(9)e44673(2012) 2.Inami, K., and Shiba, T.Syntheses of althiomycin analogs in relation to antibacterial activitiesBull. Chem. Soc. Jpn.59(7)2185-2189(1986) 3.Fujimoto, H., Kinoshita, T., Suzuki, H., et al.Studies on the mode of action of althiomycinJ. Antibiot. (Tokyo)23(6)271-275(1970)
| Cas No. | 12656-40-5 | SDF | |
| 别名 | NSC 102809 | ||
| Canonical SMILES | O=C(C1=CSC(/C=N/O)=N1)NC(CO)C2=N[C@@H](C(N3C(C=C(OC)C3)=O)=O)CS2 | ||
| 分子式 | C16H17N5O6S2 | 分子量 | 439.5 |
| 溶解度 | N/A | 储存条件 | -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 | 2.2753 mL | 11.3766 mL | 22.7531 mL |
| 5 mM | 0.4551 mL | 2.2753 mL | 4.5506 mL |
| 10 mM | 0.2275 mL | 1.1377 mL | 2.2753 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。
The insect pathogen Serratia marcescens Db10 uses a hybrid non-ribosomal peptide synthetase-polyketide synthase to produce the antibiotic Althiomycin
PLoS One 2012;7(9):e44673.PMID:23028578DOI:10.1371/journal.pone.0044673.
There is a continuing need to discover new bioactive natural products, such as antibiotics, in genetically-amenable micro-organisms. We observed that the enteric insect pathogen, Serratia marcescens Db10, produced a diffusible compound that inhibited the growth of Bacillis subtilis and Staphyloccocus aureus. Mapping the genetic locus required for this activity revealed a putative natural product biosynthetic gene cluster, further defined to a six-gene operon named alb1-alb6. Bioinformatic analysis of the proteins encoded by alb1-6 predicted a hybrid non-ribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line (Alb4/5/6), tailoring enzymes (Alb2/3) and an export/resistance protein (Alb1), and suggested that the machinery assembled Althiomycin or a related molecule. Althiomycin is a ribosome-inhibiting antibiotic whose biosynthetic machinery had been elusive for decades. Chromatographic and spectroscopic analyses confirmed that wild type S. marcescens produced Althiomycin and that production was eliminated on disruption of the alb gene cluster. Construction of mutants with in-frame deletions of specific alb genes demonstrated that Alb2-Alb5 were essential for Althiomycin production, whereas Alb6 was required for maximal production of the antibiotic. A phosphopantetheinyl transferase enzyme required for Althiomycin biosynthesis was also identified. Expression of Alb1, a predicted major facilitator superfamily efflux pump, conferred Althiomycin resistance on another, sensitive, strain of S. marcescens. This is the first report of Althiomycin production outside of the Myxobacteria or Streptomyces and paves the way for future exploitation of the biosynthetic machinery, since S. marcescens represents a convenient and tractable producing organism.
Isolation of Nannocystis species from Iran and exploring their natural products
Arch Microbiol 2022 Jan 7;204(2):123.PMID:34994917DOI:10.1007/s00203-021-02738-0.
Several different techniques were employed for the isolation of Nannocystis from various sources. A polyphasic approach was used for identification. Twelve strains of N. pusilla, N. exedens, and N. konarekensis with distinctive distribution between climates were identified. The bioactivity was examined against a panel of eight bacteria, two yeasts, and one fungus; cytotoxicity was tested on the L929 fibroblast cell line. Eleven strains mainly inhibit Gram-positive bacteria, and only one isolate was cytotoxic. The extract analyses by HPLC and LC-MS were compared to Myxobase, and eight different compounds were detected; a correlation was observed between compounds and producing species. 70% of strains had the potential to produce structurally diverse compounds. Nannochelins and Althiomycin were the most abundant metabolites. The discovery of a new species of Nannocystis and the high potentiality of strains to produce secondary metabolites encourage further sampling and in-depth analysis of extracts to find new active metabolites.
Total synthesis and semi-synthetic approaches to analogues of antibacterial natural product Althiomycin
Bioorg Med Chem Lett 2002 Feb 25;12(4):561-5.PMID:11844672DOI:10.1016/s0960-894x(01)00802-2.
Numerous analogues of the naturally occurring antibiotic Althiomycin have been synthesised exploiting both total- and semi-synthetic methodologies. The antibacterial activity of these derivatives has been determined in whole cell assays and indicates the natural product exhibits a restricted SAR.
Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
Front Bioeng Biotechnol 2019 Dec 3;7:367.PMID:31850328DOI:10.3389/fbioe.2019.00367.
Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, Althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens.
Role of the phosphopantetheinyltransferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10
Microbiology (Reading) 2014 Aug;160(Pt 8):1609-1617.PMID:24847000DOI:10.1099/mic.0.078576-0.
Phosphopantetheinyltransferase (PPTase) enzymes fulfil essential roles in primary and secondary metabolism in prokaryotes, archaea and eukaryotes. PPTase enzymes catalyse the essential modification of the carrier protein domain of fatty acid synthases, polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). In bacteria and fungi, NRPS and PKS enzymes are often responsible for the biosynthesis of secondary metabolites with clinically relevant properties; these secondary metabolites include a variety of antimicrobial peptides. We have previously shown that in the Gram-negative bacterium Serratia marcescens Db10, the PPTase enzyme PswP is essential for the biosynthesis of an NRPS-PKS dependent antibiotic called Althiomycin. In this work we utilize bioinformatic analyses to classify PswP as belonging to the F/KES subfamily of Sfp type PPTases and to putatively identify additional NRPS substrates of PswP, in addition to the Althiomycin NRPS-PKS, in Ser. marcescens Db10. We show that PswP is required for the production of three diffusible metabolites by this organism, each possessing antimicrobial activity against Staphylococcus aureus. Genetic analyses identify the three metabolites as Althiomycin, serrawettin W2 and an as-yet-uncharacterized siderophore, which may be related to enterobactin. Our results highlight the use of an individual PPTase enzyme in multiple biosynthetic pathways, each contributing to the ability of Ser. marcescens to inhibit competitor bacteria by the production of antimicrobial secondary metabolites.