Lomofungin
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| Category | Antibiotics |
| Catalog number | BBF-02656 |
| CAS | 26786-84-5 |
| Molecular Weight | 314.25 |
| Molecular Formula | C15H10N2O6 |
| Purity | >95% |
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Description
It is produced by the strain of Str. lomondensis var. lomondensis NRRL 3252. It is an antibiotic of the phenazine derivatives. It has anti-bacterial and fungal effects, but the anti-bacterial effects are weak.
Specification
| Synonyms | Lomondomycin; NSC 106995; NSC 156939; U-24792; 1-carbomethoxy-5-formyl-4,6,8-trihydroxyphenazine; 6-Formyl-4,7,9-trihydroxy-1-phenazinecarboxylic acid methyl ester |
| IUPAC Name | methyl 6-formyl-4,7,9-trihydroxy-5,9-dihydrophenazine-1-carboxylate |
| Canonical SMILES | COC(=O)C1=C2C(=NC3=C(N2)C(=O)C=C(C3=CO)O)C(=O)C=C1 |
| InChI | InChI=1S/C15H10N2O6/c1-23-15(22)6-2-3-8(19)13-11(6)16-14-10(21)4-9(20)7(5-18)12(14)17-13/h2-5,16,18,20H,1H3/b7-5+ |
| InChI Key | YDXARWIJAYOANV-FNORWQNLSA-N |
Properties
| Appearance | Olive Yellow Crystal |
| Antibiotic Activity Spectrum | Fungi |
| Boiling Point | 493.4°C at 760 mmHg |
| Melting Point | >320°C |
| Density | 1.663±0.06 g/cm3 (Predicted) |
| Solubility | Soluble in Methanol, Methanol-Hydrochloric acid, Methanol-Sodium hydroxide |
Reference Reading
1. Overexpression of afsR and Optimization of Metal Chloride to Improve Lomofungin Production in Streptomyces lomondensis S015
Wei Wang, Huasheng Wang, Hongbo Hu, Huasong Peng, Xuehong Zhang J Microbiol Biotechnol. 2015 May;25(5):672-80. doi: 10.4014/jmb.1409.09091.
As a global regulatory gene in Streptomyces, afsR can activate the biosynthesis of many secondary metabolites. The effect of afsR on the biosynthesis of a phenazine metabolite, lomofungin, was studied in Streptomyces lomondensis S015. There was a 2.5-fold increase of lomofungin production in the afsR-overexpressing strain of S. lomondensis S015 N1 compared with the wild-type strain. Meanwhile, the transcription levels of afsR and two important genes involved in the biosynthesis of lomofungin (i.e., phzC and phzE) were significantly upregulated in S. lomondensis S015 N1. The optimization of metal chlorides was investigated to further increase the production of lomofungin in the afsR-overexpressing strain. The addition of different metal chlorides to S. lomondensis S015 N1 cultivations showed that CaCl2, FeCl2, and MnCl2 led to an increase in lomofungin biosynthesis. The optimum concentrations of these metal chlorides were obtained using response surface methodology. CaCl2 (0.04 mM), FeCl2 (0.33 mM), and MnCl2 (0.38 mM) gave a maximum lomofungin production titer of 318.0 ± 10.7 mg/l, which was a 4.1-fold increase compared with that of S. lomondensis S015 N1 without the addition of a metal chloride. This work demonstrates that the biosynthesis of phenazine metabolites can be induced by afsR. The results also indicate that metal chlorides addition might be a simple and useful strategy for improving the production of other phenazine metabolites in Streptomyces.
2. Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells
Jun Arai, Kaku Goto, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato Int J Cancer. 2018 Nov 15;143(10):2575-2583. doi: 10.1002/ijc.31615. Epub 2018 Sep 22.
In our previous study on hepatocellular carcinoma (HCC) susceptibility genes in chronic hepatitis patients, we identified the MHC class I polypeptide-related sequence A (MICA). Natural killer cells eliminate various cancer cells, including HCC, by suppressing MICA shedding. Therefore, we investigated MICA sheddases and inhibitors for HCC immunotherapy. In this study, HepG2, PLC/PRF/5, and Hep3B were treated with the siRNA of a disintegrin and metalloproteases (ADAMs) and matrix metalloproteases to measure the concentration of soluble MICA (sMICA) by ELISA to detect the therapeutic target. Furthermore, an FDA-approved drug library was tested for the enzymatic inhibition of the targeted enzyme in an in vitro drug screening assay system. ADAM17 knockdown reduced sMICA levels and increased membrane-bound MICA (mMICA) expression in HCC cells. In an in vitro drug screen using an FDA-approved drug library, lomofungin, an antifungal drug, was found to strongly decrease ADAM17 activity. In HCC cells, mMICA expression was induced and sMICA production was inhibited in a dose-dependent manner. These effects were cancelled upon ADAM17 knockdown, suggesting that lomofungin targeted ADAM17. Analysis of lomofungin analogs revealed the responsible functional groups. In summary, we suggest lomofungin to be an attractive agent for the immunological control of HCC, via the suppression of ADAM17.
3. Identification of the Lomofungin Biosynthesis Gene Cluster and Associated Flavin-Dependent Monooxygenase Gene in Streptomyces lomondensis S015
Chunxiao Zhang, Chaolan Sheng, Wei Wang, Hongbo Hu, Huasong Peng, Xuehong Zhang PLoS One. 2015 Aug 25;10(8):e0136228. doi: 10.1371/journal.pone.0136228. eCollection 2015.
Streptomyces lomondensis S015 synthesizes the broad-spectrum phenazine antibiotic lomofungin. Whole genome sequencing of this strain revealed a genomic locus consisting of 23 open reading frames that includes the core phenazine biosynthesis gene cluster lphzGFEDCB. lomo10, encoding a putative flavin-dependent monooxygenase, was also identified in this locus. Inactivation of lomo10 by in-frame partial deletion resulted in the biosynthesis of a new phenazine metabolite, 1-carbomethoxy-6-formyl-4,9-dihydroxy-phenazine, along with the absence of lomofungin. This result suggests that lomo10 is responsible for the hydroxylation of lomofungin at its C-7 position. This is the first description of a phenazine hydroxylation gene in Streptomyces, and the results of this study lay the foundation for further investigation of phenazine metabolite biosynthesis in Streptomyces.
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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 ╳
