Cremimycin
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| Category | Antibiotics |
| Catalog number | BBF-01072 |
| CAS | 182285-29-6 |
| Molecular Weight | 631.79 |
| Molecular Formula | C35H53NO9 |
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Description
It is produced by the strain of Streptomyces sp. MJ635-86F6. It has anti-gram-positive bacteria activity including methicillin-resistant staphylococcus aureus (MRSA), MIC is 0.2-0.39 μg/mL. It showed cytotoxicity to mouse tumor cell lines P388, L1210, IMC, S180, B16 and SS3 in vitro.
Specification
| Synonyms | Cremimycin (antibiotic); Cyclopent(i)azacyclononadecene-7,11,17(8H,12H,19H)-trione,9,10,13,14,15,16,20,20a-octahydro-19-((2,6-dideoxy-3-O-methylhexopyranosyl)oxy)-15,18-dihydroxy-9-hexyl-2-methyl- |
| IUPAC Name | (2E,4E,6E)-10-hexyl-16,20-dihydroxy-21-(5-hydroxy-4-methoxy-6-methyloxan-2-yl)oxy-3-methyl-9-azabicyclo[17.3.0]docosa-2,4,6,19-tetraene-8,12,18-trione |
| Canonical SMILES | CCCCCCC1CC(=O)CCCC(CC(=O)C2=C(C(CC2C=C(C=CC=CC(=O)N1)C)OC3CC(C(C(O3)C)O)OC)O)O |
| InChI | InChI=1S/C35H53NO9/c1-5-6-7-8-13-25-19-26(37)14-11-15-27(38)20-28(39)33-24(17-22(2)12-9-10-16-31(40)36-25)18-30(35(33)42)45-32-21-29(43-4)34(41)23(3)44-32/h9-10,12,16-17,23-25,27,29-30,32,34,38,41-42H,5-8,11,13-15,18-21H2,1-4H3,(H,36,40)/b12-9+,16-10+,22-17+ |
| InChI Key | RUOAKWFUWPYANU-ZXGAWBIVSA-N |
Properties
| Appearance | Colorless Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Neoplastics (Tumor) |
| Boiling Point | 841.7 °C at 760 mmHg |
| Melting Point | 219-220 °C (dec.) |
| Density | 1.19 g/cm3 |
| Solubility | Soluble in Methanol, DMSO, Chloroform |
Reference Reading
1. Functional and Structural Analyses of the Split-Dehydratase Domain in the Biosynthesis of Macrolactam Polyketide Cremimycin
Daisuke Kawasaki, Akimasa Miyanaga, Taichi Chisuga, Fumitaka Kudo, Tadashi Eguchi Biochemistry. 2019 Dec 3;58(48):4799-4803. doi: 10.1021/acs.biochem.9b00897. Epub 2019 Nov 18.
In the biosynthesis of the macrolactam antibiotic cremimycin, the 3-aminononanoic acid starter unit is formed via a non-2-enoyl acyl carrier protein thioester intermediate, which is presumed to be constructed by cis-acyltransferase (AT) polyketide synthases (PKSs) CmiP2, CmiP3, and CmiP4. While canonical cis-AT PKS modules are comprised of a single polypeptide, the PKS module formed by CmiP2 and CmiP3 is split within the dehydratase (DH) domain. Here, we report the enzymatic function and the structural features of this split-DH domain. In vitro analysis showed that the split-DH domain catalyzes the dehydration reaction of (R)-3-hydroxynonanoyl N-acetylcysteamine thioester (SNAC) to form (E)-non-2-enoyl-SNAC, suggesting that the split-DH domain is catalytically active in cremimycin biosynthesis. In addition, structural analysis revealed that the CmiP2 and CmiP3 subunits of the split-DH domain form a tightly associated heterodimer through several hydrogen bonding and hydrophobic interactions, which are similar to those of canonical DH domains of other cis-AT PKSs. These results indicate that the split-DH domain has the same function and structure as common cis-AT PKS DH domains.
2. Structural Insight into the Reaction Mechanism of Ketosynthase-Like Decarboxylase in a Loading Module of Modular Polyketide Synthases
Taichi Chisuga, Akira Nagai, Akimasa Miyanaga, Ena Goto, Kosuke Kishikawa, Fumitaka Kudo, Tadashi Eguchi ACS Chem Biol. 2022 Jan 21;17(1):198-206. doi: 10.1021/acschembio.1c00856. Epub 2022 Jan 5.
Ketosynthase-like decarboxylase (KSQ) domains are widely distributed in the loading modules of modular polyketide synthases (PKSs) and are proposed to catalyze the decarboxylation of a malonyl or methylmalonyl unit for the construction of the PKS starter unit. KSQ domains have high sequence similarity to ketosynthase (KS) domains, which catalyze transacylation and decarboxylative condensation in polyketide and fatty acid biosynthesis, except that the catalytic Cys residue of KS domains is replaced by Gln in KSQ domains. Here, we present biochemical analyses of GfsA KSQ and CmiP4 KSQ, which are involved in the biosynthesis of FD-891 and cremimycin, respectively. In vitro analysis showed that these KSQ domains catalyze the decarboxylation of malonyl and methylmalonyl units. Furthermore, we determined the crystal structure of GfsA KSQ in complex with a malonyl thioester substrate analogue, which enabled identification of key amino acid residues involved in the decarboxylation reaction. The importance of these residues was confirmed by mutational analysis. On the basis of these findings, we propose a mechanism of the decarboxylation reaction catalyzed by GfsA KSQ. GfsA KSQ initiates decarboxylation by fixing the substrate in a suitable conformation for decarboxylation. The formation of enolate upon decarboxylation is assisted by two conserved threonine residues. Comparison of the structure of GfsA KSQ with those of KS domains suggests that the Gln residue in the active site of the KSQ domain mimics the acylated Cys residue in the active site of KS domains.
3. Structural Analysis of the Glycine Oxidase Homologue CmiS2 Reveals a Unique Substrate Recognition Mechanism for Formation of a β-Amino Acid Starter Unit in Cremimycin Biosynthesis
Daisuke Kawasaki, Taichi Chisuga, Akimasa Miyanaga, Fumitaka Kudo, Tadashi Eguchi Biochemistry. 2019 Jun 18;58(24):2706-2709. doi: 10.1021/acs.biochem.9b00444. Epub 2019 Jun 4.
The flavin adenine dinucleotide-dependent oxidase CmiS2 catalyzes the oxidation of N-carboxymethyl-3-aminononanoic acid to produce a 3-aminononanoic acid starter unit for the biosynthesis of cremimycin, a macrolactam polyketide. Although the sequence of CmiS2 is similar with that of the well-characterized glycine oxidase ThiO, the chemical structure of the substrate of CmiS2 is different from that of ThiO substrate glycine. Here, we present the biochemical and structural characterization of CmiS2. Kinetic analysis revealed that CmiS2 has a strong preference for N-carboxymethyl-3-aminononanoic acid over other substrates such as N-carboxymethyl-3-aminobutanoic acid and glycine, suggesting that CmiS2 recognizes the nonanoic acid moiety of the substrate as well as the glycine moiety. We determined the crystal structure of CmiS2 in complex with a substrate analogue, namely, S-carboxymethyl-3-thiononanoic acid, which enabled the identification of key amino acid residues involved in substrate recognition. We discovered that Asn49, Arg243, and Arg334 interact with the carboxyl group of the nonanoic acid moiety, while Pro46, Leu52, and Ile335 recognize the alkyl chain of the nonanoic acid moiety via hydrophobic interaction. These residues are highly conserved in CmiS2 homologues involved in the biosynthesis of related macrolactam polyketides but are not conserved in glycine oxidases such as ThiO. These results suggest that CmiS2-type enzymes employ a distinct mechanism of substrate recognition for the synthesis of β-amino acids.
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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 ╳
