Fusaricidin A

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Category Antibiotics
Catalog number BBF-01465
CAS
Molecular Weight 883.08
Molecular Formula C41H74N10O11

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Description

Fusaricidin A, a new depsipeptide antibiotic, was isolated from the culture broth of Bacillus polymyxa KT-8 obtained from the rhizosphere of garlic suffering from the basal rot caused by Fusarium oxysporum. Fusaricidin A is active against fungi and Gram-positive bacteria.

Specification

Synonyms 1-Oxa-4,7,10,13,16-pentaazacyclononadecane-6-acetamide, 18-[[15-[[(Z)-aminoiminomethyl]amino]-3-hydroxy-1-oxopentadecyl]amino]-9-[(1R)-1-hydroxyethyl]-3,19-dimethyl-12,15-bis(1-methylethyl)-2,5,8,11,1 4,17-hexaoxo-, (3R,6R,9R,12S,15R,18S,19R)-
Sequence Thr-Val-Val-Thr-Asn-Ala
IUPAC Name N-[(3R,6R,9R,12S,15R,18S,19R)-6-(2-amino-2-oxoethyl)-9-[(1R)-1-hydroxyethyl]-3,19-dimethyl-2,5,8,11,14,17-hexaoxo-12,15-di(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]-15-(diaminomethylideneamino)-3-hydroxypentadecanamide
Canonical SMILES CC1C(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)O1)C)CC(=O)N)C(C)O)C(C)C)C(C)C)NC(=O)CC(CCCCCCCCCCCCN=C(N)N)O
InChI InChI=1S/C41H74N10O11/c1-22(2)31-36(57)49-32(23(3)4)37(58)51-33(25(6)52)38(59)47-28(21-29(42)54)35(56)46-24(5)40(61)62-26(7)34(39(60)50-31)48-30(55)20-27(53)18-16-14-12-10-8-9-11-13-15-17-19-45-41(43)44/h22-28,31-34,52-53H,8-21H2,1-7H3,(H2,42,54)(H,46,56)(H,47,59)(H,48,55)(H,49,57)(H,50,60)(H,51,58)(H4,43,44,45)/t24-,25-,26-,27?,28-,31-,32+,33-,34+/m1/s1
InChI Key ZQMLIVBQFXSJNR-NVCIGDDDSA-N

Properties

Appearance Colorless Powder
Application

Fusaricidin A is a cyclic lipopeptide with potent antimicrobial properties that was originally isolated from various strains of the genus Bacillus. This natural compound has attracted great interest in drug discovery due to its broad-spectrum antimicrobial activity, low toxicity to human cells, and potential as a new therapeutic agent for drug-resistant pathogens.

Fusaricidin A is a desirable candidate for therapeutic development because it demonstrates its antibacterial action through a variety of routes. Its capacity to rupture bacterial cell membranes by creating holes, which causes cellular contents to seep out and eventually causes cell death, is one of its main routes of action. Because of its excellent membrane-targeting method, fusaricidin A is a promising broad-spectrum antibacterial drug that can combat a variety of bacteria, both Gram-positive and Gram-negative. Furthermore, it has been demonstrated that fusaricidin A inhibits the formation of bacterial cell walls by interfering with the biosynthesis of peptidoglycan, hence impairing the integrity and viability of the bacteria. Due to its twofold mode of action, fusaricidin A is a highly effective antibacterial agent that might potentially subdue pathways of antibiotic resistance that affect particular cellular functions.

Fusaricidin A is a good option for the creation of novel antibiotics to fight the growing danger of drug-resistant bacteria because of its antimicrobial qualities. In particular, fusaricidin A has proven to be highly effective against vancomycin-resistant Enterococci (VRE), multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). These findings underscore the compound's potential as a formidable tool against infectious diseases that are becoming more challenging to treat with current antibiotics. Furthermore, fusaricidin A exhibits minimal toxicity to mammalian cells, indicating a positive safety profile for possible therapeutic application. This feature indicates that fusaricidin A may be able to cure bacterial infections successfully without posing a serious risk to the host, which is important for the development of novel antimicrobial medicines.

Research on the use of Fusaricidin A in drug discovery is ongoing, with a focus on optimizing its pharmacological properties and exploring potential therapeutic applications beyond antimicrobial therapy. One area of ​​interest is the development of novel formulations and delivery systems to improve the stability and bioavailability of Fusaricidin A for systemic administration. In addition, the researchers are investigating the potential use of Fusaricidin A as a synergist in combination therapy with existing antibiotics to enhance their effectiveness against drug-resistant bacteria. By exploiting the complementary mechanisms of action of Fusaricidin A and traditional antibiotics, the researchers aim to overcome resistance mechanisms and improve treatment outcomes for patients with serious bacterial infections.

Antibiotic Activity Spectrum Gram-positive bacteria; fungi
Melting Point 201-219°C
Density 1.3±0.1 g/cm3

Reference Reading

1. Achieving Maximal Production of Fusaricidins from Paenibacillus kribbensis CU01 via Continuous Fermentation
Jaewon Ryu, Jaehoon Cho, Si Wouk Kim Appl Biochem Biotechnol. 2020 Feb;190(2):712-720. doi: 10.1007/s12010-019-03121-y. Epub 2019 Sep 2.
In this study, we investigated the potential of Paenibacillus kribbensis CU01 in producing fusaricidin, a strong antifungal substance, via optimization of metal ions and carbon and nitrogen source, and continuous fermentation. In the cultivation of a 2-l batch, maximal production of fusaricidins (581 mg l-1) was achieved in a modified M9 medium containing metal ions, 10 g l-1 glucose, and 1 g l-1 ammonium chloride. Most of glucose was consumed at a rate of 0.74 g l-1 h-1 within 24 h and fusaricidin production began 15 h after batch cultivation. Continuous fermentation was performed using a 7-l fermenter with 2-l working volume of modified M9 medium containing 10 g l-1 glucose, 1 × 10-3 M FeSO4, and 1 × 10-6 M MnCl2. After 24 h of the start of cultivation, fresh M9 medium was continuously supplied at a flow rate of 2.5 ml min-1, and simultaneously, the same amount of cell culture broth was removed. In a continuous system, the highest fusaricidin concentration (579 mg l-1) was obtained using a dilution rate of 0.075 h-1 with an average productivity of 10.4 mg l-1 h-1 for 24 to 72 h of incubation. Based on these results, it was found that fusaricidin production using P. kribbens CU01 strain increased by at least 28 times the values reported in previous studies.
2. Genomics assisted functional characterization of Paenibacillus polymyxa HK4 as a biocontrol and plant growth promoting bacterium
Riteshri Soni, Khushboo Rawal, Hareshkumar Keharia Microbiol Res. 2021 Jul;248:126734. doi: 10.1016/j.micres.2021.126734. Epub 2021 Mar 1.
The diseases caused by phytopathogens account for huge economic losses in the agricultural sector. Paenibacillus polymyxa is one of the agriculturally important biocontrol agents and plant growth promoting bacterium. This study describes the antifungal potential of P. polymyxa HK4 against an array of fungal phytopathogens and its ability to stimulate seed germination of cumin and groundnut under in vitro conditions. The cumin and groundnut seeds bacterized with HK4 exhibited enhanced germination efficiency in comparison to controls. The use of HK4 as a soil inoculant significantly promoted the shoot length and fresh weight of groundnut plants in pot studies. The draft genome analysis of HK4 revealed the genetic attributes for motility, root colonization, antagonism, phosphate solubilization, siderophore production and production of volatile organic compounds. The bacterium HK4 harnessed several hydrolytic enzymes that may assist its competence in the rhizosphere. The PCR amplification and sequence analysis of the conserved region of the fusA gene amplicon revealed the ability of HK4 to produce fusaricidin. Furthermore, the LC-ESI-MS/MS of crude cell pellet extract of HK4 confirmed the presence of fusaricidin as a major antifungal metabolite. This study demonstrated the potential of HK4 as a biocontrol agent and a plant growth promoter.
3. Isolation and Characterization of a New Fusaricidin-Type Antibiotic Produced by Paenibacillus bovis sp. nov BD3526
Bangqing Hua, Huafeng Feng, Jin Han, Zhenyi Qiao, Xiaohua Wang, Qiuxiang Zhang, Zhenmin Liu, Zhengjun Wu Curr Microbiol. 2020 Dec;77(12):3990-3999. doi: 10.1007/s00284-020-02206-w. Epub 2020 Oct 12.
Paenibacillus bovis sp. nov BD3526, isolated from raw yak (Bos grunniens) milk, was able to produce antibacterial substances against Micrococcus luteus. The antibacterial substances produced by the strain BD3526 in 3% (w/v) wheat bran broth under aerobic conditions were precipitated from the cultivated broth with ammonium sulfate at 60% saturation. Two antibacterial compounds were obtained by Sephadex LH-20 chromatography and semi-preparative reverse-phase high-performance liquid chromatography (Semi-Pre RP-HPLC). The chemical structures of the two antibacterial compounds were further elucidated by means of ultra high-performance liquid chromatography-mass spectrometer/mass spectrometer (UHPLC-MS/MS). One compound, with a molecular mass of 883.56195 Da (M + H)+, was determined to be identical in chemical structure with that of the well-known compound fusaricidin A. The other antimicrobial compound with a molecular mass of 911.59393 Da (M + H)+ was determined to be a derivative of fusaricidin A by tandem mass spectrometry and amino acid composition analysis and was designed as bovisin. Bovisin possessed the stability against acid/alkali, heat and some proteases treatment, the same with the fusaricidin A. However, the minimal inhibition concentration (MIC) of bovisin on the tested indicator including Staphylococcus aureus, Micrococcus luteus, Listeria monocytogenes and Bacillus subtilis were 50, 50, 50, 50 μg/mL, respectively, slightly higher than those of fusaricidin A (6.25, 6.25, 6.25, 12.5 μg/mL), indicating bovisin with a weaker inhibitory activity.

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