Cremeomycin
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| Category | Antibiotics |
| Catalog number | BBF-01071 |
| CAS | |
| Molecular Weight | 194.14 |
| Molecular Formula | C8H6N2O4 |
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Description
It is produced by the strain of Streptomyces cremeus. It has anti-gram-positive bacteria, negative bacteria, fungi (weak) activity, and has the effect of inhibiting the leukemic cell L-1210 (IC50 is 1.5 μg/mL).
Specification
| Synonyms | Antibiotic U-23643 |
| IUPAC Name | 6-carboxy-2-diazonio-3-methoxyphenolate |
| Canonical SMILES | COC1=C(C(=C(C=C1)C(=O)O)[O-])[N+]#N |
| InChI | InChI=1S/C8H6N2O4/c1-14-5-3-2-4(8(12)13)7(11)6(5)10-9/h2-3H,1H3,(H-,11,12,13) |
| InChI Key | IGWQRYHQYGPQLO-UHFFFAOYSA-N |
Properties
| Appearance | Yellow Solid |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria; Fungi; Neoplastics (Tumor) |
| Melting Point | 142-143 °C |
| Solubility | Soluble in Water, Methanol, Acetone, Ethyl Acetate, Dichloromethane, Ethyl Ether; Insoluble in Petroleum Ether |
Reference Reading
1. Discovery of a Diazo-Forming Enzyme in Cremeomycin Biosynthesis
Abraham J Waldman, Emily P Balskus J Org Chem. 2018 Jul 20;83(14):7539-7546. doi: 10.1021/acs.joc.8b00367. Epub 2018 May 29.
The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show that the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology as well as enable genome-based discovery of new diazo-containing metabolites.
2. Novel desferrioxamine derivatives synthesized using the secondary metabolism-specific nitrous acid biosynthetic pathway in Streptomyces davawensis
Ryota Hagihara, Yohei Katsuyama, Yoshinori Sugai, Hiroyasu Onaka, Yasuo Ohnishi J Antibiot (Tokyo). 2018 Nov;71(11):911-919. doi: 10.1038/s41429-018-0088-1. Epub 2018 Aug 17.
Recently, a novel nitrous acid biosynthetic pathway composed of two enzymes was discovered to be involved in the biosynthesis of cremeomycin for the formation of its diazo group. In this pathway, CreE oxidizes L-aspartic acid to nitrosuccinic acid and CreD liberates nitrous acid from nitrosuccinic acid. Bioinformatic analysis showed that various actinobacteria have putative secondary metabolite biosynthesis gene clusters containing creE and creD homologs, suggesting that this pathway is widely used for the biosynthesis of various natural products. Here, we focused on creE and creD homologs (BN159_4422 and BN159_4421) in Streptomyces davawensis. In vitro analysis of recombinant BN159_4422 and BN159_4421 proteins showed that these enzymes synthesized nitrous acid from L-aspartic acid. Secondary metabolites produced by this gene cluster were investigated by comparing the metabolic profiles of the wild-type and ΔBN159_4422 strains. When these strains were co-cultured with Tsukamurella pulmonis TP-B0596, three compounds were specifically produced by the wild-type strain. These compounds were identified as novel desferrioxamine derivatives containing either of two unique five-membered heterocyclic ring structures and shown to have iron-binding properties. A putative desferrioxamine biosynthetic gene cluster was found in the S. davawensis genome, and inactivation of a desD homolog (BN159_5485) also abolished the production of these compounds. We propose that these compounds should be synthesized by the modification of desferrioxamine B and a shorter chain analog using nitrous acid produced by the CreE and CreD homologs. This study provides an important insight into the diverse usage of the secondary metabolism-specific nitrous acid biosynthetic pathway in actinomycetes.
3. Crystal structure of the nitrosuccinate lyase CreD in complex with fumarate provides insights into the catalytic mechanism for nitrous acid elimination
Yohei Katsuyama, Yukari Sato, Yoshinori Sugai, Yousuke Higashiyama, Miki Senda, Toshiya Senda, Yasuo Ohnishi FEBS J. 2018 Apr;285(8):1540-1555. doi: 10.1111/febs.14429. Epub 2018 Mar 24.
Enzymes belonging to the aspartase/fumarase superfamily catalyze elimination of various functional groups from succinate derivatives and play an important role in primary metabolism and aromatic compound degradation. Recently, an aspartase/fumarase superfamily enzyme, CreD, was discovered in cremeomycin biosynthesis. This enzyme catalyzes the elimination of nitrous acid from nitrosuccinate synthesized from aspartate by CreE, a flavin-dependent monooxygenase. Nitrous acid generated by this pathway is an important precursor of the diazo group of cremeomycin. CreD is the first aspartase/fumarase superfamily enzyme that was reported to catalyze the elimination of nitrous acid, and therefore we aimed to analyze its reaction mechanism. The crystal structure of CreD was determined by the molecular replacement native-single anomalous diffraction method at 2.18 Å resolution. Subsequently, the CreD-fumarate complex structure was determined at 2.30 Å resolution by the soaking method. Similar to other aspartase/fumarase superfamily enzymes, the crystal structure of CreD was composed of three domains and formed a tetramer. Two molecules of fumarate were observed in one subunit of the CreD-fumarate complex. One of them was located in the active site pocket formed by three different subunits. Intriguingly, no histidine residue, which usually functions as a catalytic acid in aspartase/fumarase superfamily enzymes, was found around the fumarate molecule in the active site. Based on the mutational analysis, we propose a catalytic mechanism of CreD, in which Arg325 acts as a catalytic acid. Databases: The crystal structures of CreD and the CreD-fumarate complex were deposited to PDB under the accession numbers 5XNY and 5XNZ, respectively. Enzymes: Nitrosuccinate lyase CreD, EC4.3.
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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 ╳
