Cyclothiazomycin
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| Category | Enzyme inhibitors |
| Catalog number | BBF-01123 |
| CAS | 133352-26-8 |
| Molecular Weight | 1473.71 |
| Molecular Formula | C59H64N18O14S7 |
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Description
It is produced by the strain of Streptomyces sp. NR0516. It selectively inhibits renin activity and does not inhibit pepsin, aspartic acid, serine, mercaptan protease and metalloproteinases. In addition, it has weak antifungal activity.
Specification
| Synonyms | cyclothiazomycin A; 5102-II |
| IUPAC Name | (12R,27S,30R,33S,36S,42Z,48S,51R,55S,59R,62Z)-55-(2-amino-2-oxoethyl)-42,62-di(ethylidene)-36-[(1R)-1-hydroxyethyl]-33,51-dimethyl-15-methylidene-13,28,34,37,40,43,49,53,60,63-decaoxo-6,10,17,21,25,32,57-heptathia-14,29,35,38,41,44,50,54,61,64,65,66,67,68,69,70,71-heptadecazadecacyclo[31.19.12.14,52.15,8.19,12.116,19.120,23.124,27.156,59.044,48]henheptaconta-1(52),2,4(66),5(71),7,9(70),16(69),18,20(68),22,24(67),56(65)-dodecaene-30-carboxylic acid |
| Canonical SMILES | CC=C1C(=O)NC2(C(=O)NC(C(=O)NCC(=O)NC(=CC)C(=O)N3CCCC3C(=O)NC(C4=C(C=CC(=N4)C5=NC(=CS5)C6=NC(CS6)C(=O)NC(=C)C7=NC(=CS7)C8=NC(=CS8)C9=NC(CS9)C(=O)NC(CS2)C(=O)O)C(=O)NC(C2=NC(CS2)C(=O)N1)CC(=O)N)C)C(C)O)C |
| InChI | InChI=1S/C59H64N18O14S7/c1-7-27-47(85)76-59(6)58(91)75-42(25(5)78)49(87)61-15-40(80)64-28(8-2)56(88)77-13-9-10-38(77)48(86)62-23(3)41-26(43(81)67-30(14-39(60)79)52-69-32(17-93-52)45(83)66-27)11-12-29(65-41)51-73-35(20-96-51)53-70-31(16-94-53)44(82)63-24(4)50-72-34(19-92-50)55-74-36(21-97-55)54-71-33(18-95-54)46(84)68-37(22-98-59)57(89)90/h7-8,11-12,19-21,23,25,30-33,37-38,42,78H,4,9-10,13-18,22H2,1-3,5-6H3,(H2,60,79)(H,61,87)(H,62,86)(H,63,82)(H,64,80)(H,66,83)(H,67,81)(H,68,84)(H,75,91)(H,76,85)(H,89,90)/b27-7-,28-8-/t23-,25-,30+,31+,32+,33-,37+,38+,42+,59+/m1/s1 |
| InChI Key | OGUUCNCVZHZWGA-CRYGVMHLSA-N |
Properties
| Appearance | Light Brown Amorphous Powder |
| Antibiotic Activity Spectrum | Fungi |
| Melting Point | > 210 °C (dec.) |
| Solubility | Soluble in Water, Methanol, Chloroform |
Reference Reading
1. Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008
Peipei Zhang, Hang Wu, Xiu-Lan Chen, Zixin Deng, Linquan Bai, Xiuhua Pang Microbiology (Reading). 2014 Jul;160(Pt 7):1379-1392. doi: 10.1099/mic.0.076901-0. Epub 2014 Apr 25.
Cyclothiazomycin is a member of the thiopeptide antibiotics, which are usually complicated derivatives of ribosomally synthesized peptides. A gene cluster containing 12 ORFs identical to the clt cluster encoding cyclothiazomycin from Streptomyces hygroscopicus 10-22 was revealed by genome sequencing in S. hygroscopicus 5008. Genes SHJG8833 and SHJG8837 of the cluster and flanking gene SHJG8838 were predicted to encode regulatory proteins from different families. In this study, we showed that the newly identified cluster is functional and we investigated the roles of these regulatory genes in the regulation of cyclothiazomycin biosynthesis. We determined that SHJG8833, but not SHJG8837 or SHJG8838, is critical for cyclothiazomycin biosynthesis. The transcriptional start point of SHJG8833 was located to a thymidine 54 nt upstream of the start codon. Inactivation of SHJG8833 abrogated the production of cyclothiazomycin, and synthesis could be restored by reintroducing SHJG8833 into the mutant strain. Gene expression analyses indicated that SHJG8833 regulates a consecutive set of seven genes from SHJG8826 to SHJG8832, whose products are predicted to be involved in different steps in the construction of the main framework of cyclothiazomycin. Transcriptional analysis indicated that these seven genes may form two operons, SHJG8826-27 and SHJG8828-32. Gel-shift analysis demonstrated that the DNA-binding domain of SHJG8833 binds the promoters of SHJG8826 and SHJG8828 and sequences internal to SHJG8826 and SHJG8829, and a conserved binding sequence was deduced. These results indicate that SHJG8833 is a positive regulator that controls cyclothiazomycin biosynthesis by activating structural genes in the clt cluster.
2. IBX mediated reaction of β-enamino esters with allylic alcohols: a one pot metal free domino approach to functionalized pyridines
Narendar Reddy Gade, V Devendram, Manojit Pal, Javed Iqbal Chem Commun (Camb). 2013 Sep 18;49(72):7926-8. doi: 10.1039/c3cc44274h. Epub 2013 Jul 30.
IBX facilitated the reaction of β-enamino esters with allylic alcohols affording a direct, one-pot and metal free synthesis of functionalized pyridines including 2-substituted nicotinic acids, densely substituted pyridines and precursors of azafluorenones. The methodology also afforded the racemic pyridine core of cyclothiazomycin.
3. Nucleophilic 1,4-additions for natural product discovery
Courtney L Cox, Jonathan I Tietz, Karol Sokolowski, Joel O Melby, James R Doroghazi, Douglas A Mitchell ACS Chem Biol. 2014 Sep 19;9(9):2014-22. doi: 10.1021/cb500324n. Epub 2014 Jun 17.
Natural products remain an important source of drug candidates, but the difficulties inherent to traditional isolation, coupled with unacceptably high rates of compound rediscovery, limit the pace of natural product detection. Here we describe a reactivity-based screening method to rapidly identify exported bacterial metabolites that contain dehydrated amino acids (i.e., carbonyl- or imine-activated alkenes), a common motif in several classes of natural products. Our strategy entails the use of a commercially available thiol, dithiothreitol, for the covalent labeling of activated alkenes by nucleophilic 1,4-addition. Modification is easily discerned by comparing mass spectra of reacted and unreacted cell surface extracts. When combined with bioinformatic analysis of putative natural product gene clusters, targeted screening and isolation can be performed on a prioritized list of strains. Moreover, known compounds are easily dereplicated, effectively eliminating superfluous isolation and characterization. As a proof of principle, this labeling method was used to identify known natural products belonging to the thiopeptide, lanthipeptide, and linaridin classes. Further, upon screening a panel of only 23 actinomycetes, we discovered and characterized a novel thiopeptide antibiotic, cyclothiazomycin C.
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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 ╳
