Yatakemycin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-02980 |
| CAS | 606136-98-5 |
| Molecular Weight | 679.70 |
| Molecular Formula | C35H29N5O8S |
Online Inquiry
Description
It is an antifungal antibiotic produced by the strain of Streptomyces sp. TP-A0356. Its anti-fungal activity against Aspergillus fumigatus, Aspergillus flavus, Aspergillus Niger, Candida albicans and Cryptococcus neoformans is stronger than Amphotericin B and Etraconazole (MIC is 0.0039-0.0156 μg/mL). It also has strong cytotoxicity to P388, HeLa, HEL and other tumor cells (IC50 is 0.01-0.33 μg/mL).
Specification
| Synonyms | (+)-yatakemycin; Ethanethioic acid, S-(6-(((7bR,8aS)-1,2,4,5,8,8a-hexahydro-2-((6-hydroxy-5-methoxy-1H-indol-2-yl)carbonyl)-4-oxocyclopropa(c)pyrrolo(3,2-e)indol-6-yl)carbonyl)-3,6,7,8-tetrahydro-5-hydroxy-4-methoxybenzo(1,2-b:4,3-b')dipyrrol-2-yl) ester |
| IUPAC Name | S-methyl 5-hydroxy-6-[(1R,12S)-10-(5-hydroxy-6-methoxy-1H-indole-2-carbonyl)-7-oxo-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-4-carbonyl]-4-methoxy-7,8-dihydro-3H-pyrrolo[3,2-e]indole-2-carbothioate |
| Canonical SMILES | COC1=C(C=C2C=C(NC2=C1)C(=O)N3CC4CC45C3=CC(=O)C6=C5C=C(N6)C(=O)N7CCC8=C9C=C(NC9=C(C(=C87)O)OC)C(=O)SC)O |
| InChI | InChI=1S/C35H29N5O8S/c1-47-25-10-19-14(7-23(25)41)6-20(36-19)33(45)40-13-15-12-35(15)18-9-21(37-28(18)24(42)11-26(35)40)32(44)39-5-4-16-17-8-22(34(46)49-3)38-27(17)31(48-2)30(43)29(16)39/h6-11,15,36-38,41,43H,4-5,12-13H2,1-3H3/t15-,35-/m1/s1 |
| InChI Key | CMFSXTISUXTEGX-QXPWRNTLSA-N |
Properties
| Appearance | Yellow Powder |
| Antibiotic Activity Spectrum | Neoplastics (Tumor); Fungi |
| Melting Point | >220°C (dec.) |
| Density | 1.7±0.1 g/cm3 |
| Solubility | Soluble in Methanol, DMF |
Reference Reading
1. Insights into conformational changes in AlkD bound to DNA with a yatakemycin adduct from computational simulations
Pavel Silvestrov, G Andrés Cisneros Theor Chem Acc. 2018 Jun;137:78. Epub 2018 May 12.
Structural integrity of DNA molecules is necessary for their information storage function. Cells rely on a number of pathways to ensure that the damage to DNA induced by endogenous and exogenous reagents is repaired. AlkD, a base excision enzyme, removes a damaged nucleobase by cleaving a glycosidic bond. Unlike many other base excision enzymes, AlkD does not flip a damaged nucleobase into a designated reaction pocket, and as such can repair nucleobases with larger adducts, such as yatakemycin. In this study, the structure and dynamics of AlkD have been investigated by classical molecular dynamics simulations. Several systems including apo-AlkD, and AlkD in complex with DNA, both with and without the yatakemycin adduct have been simulated. Comparison of the results for the apo-AlkD with AlkD with substrate (damaged or undamaged) indicates a high degree of motion of helix αB in apo-AlkD, whereas this helix is observed to form various contacts when the substrate is bound. The calculated results are consistent with previous experimental studies that have suggested various residues involved in damage recognition, DNA binding, and base excision catalysis.
2. Structural evolution of a DNA repair self-resistance mechanism targeting genotoxic secondary metabolites
Elwood A Mullins, Jonathan Dorival, Gong-Li Tang, Dale L Boger, Brandt F Eichman Nat Commun. 2021 Nov 26;12(1):6942. doi: 10.1038/s41467-021-27284-7.
Microbes produce a broad spectrum of antibiotic natural products, including many DNA-damaging genotoxins. Among the most potent of these are DNA alkylating agents in the spirocyclopropylcyclohexadienone (SCPCHD) family, which includes the duocarmycins, CC-1065, gilvusmycin, and yatakemycin. The yatakemycin biosynthesis cluster in Streptomyces sp. TP-A0356 contains an AlkD-related DNA glycosylase, YtkR2, that serves as a self-resistance mechanism against yatakemycin toxicity. We previously reported that AlkD, which is not present in an SCPCHD producer, provides only limited resistance against yatakemycin. We now show that YtkR2 and C10R5, a previously uncharacterized homolog found in the CC-1065 biosynthetic gene cluster of Streptomyces zelensis, confer far greater resistance against their respective SCPCHD natural products. We identify a structural basis for substrate specificity across gene clusters and show a correlation between in vivo resistance and in vitro enzymatic activity indicating that reduced product affinity-not enhanced substrate recognition-is the evolutionary outcome of selective pressure to provide self-resistance against yatakemycin and CC-1065.
3. Toxicity and repair of DNA adducts produced by the natural product yatakemycin
Elwood A Mullins, Rongxin Shi, Brandt F Eichman Nat Chem Biol. 2017 Sep;13(9):1002-1008. doi: 10.1038/nchembio.2439. Epub 2017 Jul 24.
Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and is the most recent addition to the CC-1065 and duocarmycin family of natural products. Though bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide-excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base-excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for the way they are eliminated by BER have been unclear. Here, we describe the structural and biochemical properties of YTM adducts that are responsible for their toxicity, and define the mechanism by which they are excised by AlkD. These findings delineate an alternative strategy for repair of bulky DNA damage and establish the cellular utility of this pathway relative to that of NER.
Recommended Products
| BBF-00764 | Cerebroside C | Inquiry |
| BBF-01825 | Loganin | Inquiry |
| BBF-03753 | Baicalin | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-03755 | Actinomycin D | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
