Cepafungin I
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| Category | Antibiotics |
| Catalog number | BBF-00211 |
| CAS | 130743-08-7 |
| Molecular Weight | 534.67 |
| Molecular Formula | C28H46N4O6 |
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Description
Cepafungin I is an acyl peptide antibiotic produced by Pseudomonas sp. CB-3. It has activity against Candida, Aspergillus fumigatus and Trichophyton, but it is not effective against Candida albicans M-9 infection in mice.
Specification
| Synonyms | 2,4-Dodecadienamide, N-(2-hydroxy-1-(((10-hydroxy-5-methyl-2,7-dioxo-1,6-diazabicyclododec-3-en-8-yl)amino)carbonyl)propyl)-11-methyl-, (5S-(3E,5R*,8R*(1R*(2E,4E),2S*),10R*))- |
| IUPAC Name | (2E,4E)-N-[(2S,3R)-3-hydroxy-1-[[(3Z,5S,8S,10S)-10-hydroxy-5-methyl-2,7-dioxo-1,6-diazacyclododec-3-en-8-yl]amino]-1-oxobutan-2-yl]-11-methyldodeca-2,4-dienamide |
| Canonical SMILES | CC1C=CC(=O)NCCC(CC(C(=O)N1)NC(=O)C(C(C)O)NC(=O)C=CC=CCCCCCC(C)C)O |
| InChI | InChI=1S/C28H46N4O6/c1-19(2)12-10-8-6-5-7-9-11-13-25(36)32-26(21(4)33)28(38)31-23-18-22(34)16-17-29-24(35)15-14-20(3)30-27(23)37/h7,9,11,13-15,19-23,26,33-34H,5-6,8,10,12,16-18H2,1-4H3,(H,29,35)(H,30,37)(H,31,38)(H,32,36)/b9-7+,13-11+,15-14-/t20-,21+,22-,23-,26-/m0/s1 |
| InChI Key | SVHNVAFCZJDSIW-VBFMYEFXSA-N |
Properties
| Antibiotic Activity Spectrum | fungi |
| Boiling Point | 890.2°C at 760 mmHg |
| Melting Point | 235-240°C |
| Density | 1.15 g/cm3 |
Reference Reading
1. Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations
Alexander Amatuni, Anton Shuster, Daniel Abegg, Alexander Adibekian, Hans Renata ACS Cent Sci. 2023 Jan 27;9(2):239-251. doi: 10.1021/acscentsci.2c01219. eCollection 2023 Feb 22.
The cepafungins are a class of highly potent and selective eukaryotic proteasome inhibitor natural products with potential to treat refractory multiple myeloma and other cancers. The structure-activity relationship of the cepafungins is not fully understood. This Article chronicles the development of a chemoenzymatic approach to cepafungin I. A failed initial route involving derivatization of pipecolic acid prompted us to examine the biosynthetic pathway for the production of 4-hydroxylysine, which culminated in the development of a 9-step synthesis of cepafungin I. An alkyne-tagged analogue enabled chemoproteomic studies of cepafungin and comparison of its effects on global protein expression in human multiple myeloma cells to the clinical drug bortezomib. A preliminary series of analogues elucidated critical determinants of potency in proteasome inhibition. Herein we report the chemoenzymatic syntheses of 13 additional analogues of cepafungin I guided by a proteasome-bound crystal structure, 5 of which are more potent than the natural product. The lead analogue was found to have 7-fold greater proteasome β5 subunit inhibitory activity and has been evaluated against several multiple myeloma and mantle cell lymphoma cell lines in comparison to the clinical drug bortezomib.
2. Evaluation of the Antifungal Activities of Photorhabdus akhurstii and Its Secondary Metabolites against Phytopathogenic Colletotrichum gloeosporioides
Po-Wen Tu, Jie-Siang Chiu, Chih Lin, Chih-Cheng Chien, Feng-Chia Hsieh, Ming-Che Shih, Yu-Liang Yang J Fungi (Basel). 2022 Apr 15;8(4):403. doi: 10.3390/jof8040403.
Colletotrichum gloeosporioides is a phytopathogenic fungus that causes devastating losses in strawberries without effective countermeasures. Members of the genus Photorhabdus exhibit antimicrobial capability and have been found to have the potential for use as biocontrol agents against C. gloeosporioides. Photorhabdus species exhibit two phase variations with a differentiated composition of secondary metabolites designated to each phase. In this study, Photorhabdus akhurstii sp. nov. 0813-124 exhibited phase I (PL1) and phase II (PL2); however, only PL1 displayed distinct inhibition of C. gloeosporioides in the confrontation assay. We identified the bioactive ingredients of P. akhurstii sp. nov. 0813-124 to be glidobactin A and cepafungin I, with MIC values lower than 1.5 and 2.0 µg/mL, respectively. Furthermore, we revealed the biosynthetic gene cluster (BGC) of corresponding bioactive molecules through genomics analysis and determined its expression level in PL1 and PL2. The expression of glidobactin BGC in PL1 increased rapidly within 24 h, while PL2 was eventually stimulated after 60 h. In summary, we demonstrated that P. akhurstii sp. nov. 0813-124 could potentially be used as a biocontrol agent or part of a natural product repertoire for combating C. gloeosporioides.
3. Activation, Structure, Biosynthesis and Bioactivity of Glidobactin-like Proteasome Inhibitors from Photorhabdus laumondii
Lei Zhao, Camille Le Chapelain, Alexander O Brachmann, Marcel Kaiser, Michael Groll, Helge B Bode Chembiochem. 2021 May 4;22(9):1582-1588. doi: 10.1002/cbic.202100014. Epub 2021 Mar 3.
The glidobactin-like natural products (GLNPs) glidobactin A and cepafungin I have been reported to be potent proteasome inhibitors and are regarded as promising candidates for anticancer drug development. Their biosynthetic gene cluster (BGC) plu1881-1877 is present in entomopathogenic Photorhabdus laumondii but silent under standard laboratory conditions. Here we show the largest subset of GLNPs, which are produced and identified after activation of the silent BGC in the native host and following heterologous expression of the BGC in Escherichia coli. Their chemical diversity results from a relaxed substrate specificity and flexible product release in the assembly line of GLNPs. Crystal structure analysis of the yeast proteasome in complex with new GLNPs suggests that the degree of unsaturation and the length of the aliphatic tail are critical for their bioactivity. The results in this study provide the basis to engineer the BGC for the generation of new GLNPs and to optimize these natural products resulting in potential drugs for cancer therapy.
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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 ╳
