Tirandamycin A
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-03419 |
| CAS | 34429-70-4 |
| Molecular Weight | 417.45 |
| Molecular Formula | C22H27NO7 |
| Purity | 95% by HPLC |
Online Inquiry
Description
Tirandamycin A is originally isolated from Str. tirandis var. tirandis NRRL 3689, and it has anti-gram-positive bacteria effect.
Specification
| Synonyms | NSC 107067; 3-Pyrrolin-2-one, 4-hydroxy-3-(4-methyl-6-(1,2,7-trimethyl-5-oxo-3,9,10-trioxatricyclo(4.3.1.0(sup 2,4))dec-8-yl)-2,4-heptadienoyl)-, (E,E)- |
| Storage | Store at-20°C |
| IUPAC Name | (3E)-3-[(2E,4E,6R)-1-hydroxy-4-methyl-6-[(1R,2S,4R,6R,7R,8R)-1,2,7-trimethyl-5-oxo-3,9,10-trioxatricyclo[4.3.1.02,4]decan-8-yl]hepta-2,4-dienylidene]pyrrolidine-2,4-dione |
| Canonical SMILES | CC1C2C(=O)C3C(O3)(C(O2)(OC1C(C)C=C(C)C=CC(=C4C(=O)CNC4=O)O)C)C |
| InChI | InChI=1S/C22H27NO7/c1-10(6-7-13(24)15-14(25)9-23-20(15)27)8-11(2)17-12(3)18-16(26)19-21(4,30-19)22(5,28-17)29-18/h6-8,11-12,17-19,24H,9H2,1-5H3,(H,23,27)/b7-6+,10-8+,15-13+/t11-,12-,17-,18-,19+,21+,22-/m1/s1 |
| InChI Key | URGUBECARCAPRI-UYXUTHQNSA-N |
Properties
| Appearance | Yellow Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Boiling Point | 639.1±55.0°C at 760 mmHg |
| Density | 1.3±0.1 g/cm3 |
| Solubility | Soluble in Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc. |
Reference Reading
1. A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298
Xin Zhen, Ting Gong, Fu Liu, Pei-Cheng Zhang, Wan-Qi Zhou, Yan Li, Ping Zhu Mar Drugs. 2015 Nov 18;13(11):6947-61. doi: 10.3390/md13116947.
Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey's method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.
2. Δ(11,12) double bond formation in tirandamycin biosynthesis is atypically catalyzed by TrdE, a glycoside hydrolase family enzyme
Xuhua Mo, Junying Ma, Hongbo Huang, Bo Wang, Yongxiang Song, Si Zhang, Changsheng Zhang, Jianhua Ju J Am Chem Soc. 2012 Feb 15;134(6):2844-7. doi: 10.1021/ja206713a. Epub 2012 Feb 1.
The tirandamycins (TAMs) are a small group of Streptomyces-derived natural products that target bacterial RNA polymerase. Within the TAM biosynthetic cluster, trdE encodes a glycoside hydrolase whose role in TAM biosynthesis has been undefined until now. We report that in vivo trdE inactivation leads to accumulation of pre-tirandamycin, the earliest intermediate released from its mixed polyketide/nonribosomal peptide biosynthetic assembly line. In vitro and site-directed mutagenesis studies showed that TrdE, a putative glycoside hydrolase, catalyzes in a highly atypical fashion the installation of the Δ(11,12) double bond during TAM biosynthesis.
3. Molecular Basis of Iterative C-H Oxidation by TamI, a Multifunctional P450 monooxygenase from the Tirandamycin Biosynthetic Pathway
Sean A Newmister, Kinshuk Raj Srivastava, Rosa V Espinoza, Kersti Caddell Haatveit, Yogan Khatri, Rachel M Martini, Marc Garcia-Borràs, Larissa M Podust, K N Houk, David H Sherman ACS Catal. 2020 Nov 20;10(22):13445-13454. doi: 10.1021/acscatal.0c03248. Epub 2020 Nov 4.
Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.
Recommended Products
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-03753 | Baicalin | Inquiry |
| BBF-03755 | Actinomycin D | 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 ╳
