Fengycin

• CAT Number: M000908
• CAS Number: 102577-03-7
• Molecular Formula: C10H16OSi
• Molecular Weight: 1463.7
• Purity: ≥95%
• Synonyms: Fengycin C; Fengymycin.
• Storage: -80°C
• IUPAC Name: (4S)-5-[[(2R)-5-amino-1-[[(4S,7S,10S,13S,19R,22S,25S,28R)-10-(3-amino-3-oxopropyl)-4-[(2R)-butan-2-yl]-22-(2-carboxyethyl)-25-[(1S)-1-hydroxyethyl]-7-[(4-hydroxyphenyl)methyl]-19-methyl-3,6,9,12,18,21,24,27-octaoxo-2-oxa-5,8,11,17,20,23,26-heptazatricyclo[28.2.2.013,17]tetratriaconta-1(33),30(34),31-trien-28-yl]amino]-1-oxopentan-2-yl]amino]-4-(3-hydroxyhexadecanoylamino)-5-oxopentanoic acid
• InChI: InChI=1S/C72H110N12O20/c1-6-8-9-10-11-12-13-14-15-16-17-20-48(87)41-58(89)76-51(32-35-59(90)91)65(96)77-50(21-18-37-73)64(95)80-55-40-46-25-29-49(30-26-46)104-72(103)61(42(3)7-2)82-67(98)54(39-45-23-27-47(86)28-24-45)81-66(97)52(31-34-57(74)88)78-69(100)56-22-19-38-84(56)71(102)43(4)75-63(94)53(33-36-60(92)93)79-70(101)62(44(5)85)83-68(55)99/h23-30,42-44,48,50-56,61-62,85-87H,6-22,31-41,73H2,1-5H3,(H2,74,88)(H,75,94)(H,76,89)(H,77,96)(H,78,100)(H,79,101)(H,80,95)(H,81,97)(H,82,98)(H,83,99)(H,90,91)(H,92,93)/t42-,43-,44+,48?,50-,51+,52+,53+,54+,55-,56+,61+,62+/m1/s1
• InChIKey: CUOJDWBMJMRDHN-RLLVTFBRSA-N
• SMILES: CCCCCCCCCCCCCC(CC(=O)NC(CCC(=O)O)C(=O)NC(CCCN)C(=O)NC1CC2=CC=C(C=C2)OC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C3CCCN3C(=O)C(NC(=O)C(NC(=O)C(NC1=O)C(C)O)CCC(=O)O)C)CCC(=O)N)CC4=CC=C(C=C4)O)C(C)CC)O

Fengycin(CAS: 102577-03-7) is a lipopeptide complex which is synthesized by Bacillus subtilis strain F-29-3. It is an antifungal compound, and is made up of two components namely, fengycin A and fengycin B. Fengycin A contains 1 D-Ala, 1 L-Ile, 1 L-Pro, 1 D-allo-Thr, 3 L-Glx, 1 D-Tyr, 1 L-Tyr, 1 D-Orn, whereas fengycin B contains D-Val instead of D-Ala. Fengycin may be used for the sterilization of E. coli., and for the inactivation of spores of Bacillus cereus.
Fengycin shows antifungal properties against filamentous fungi, but has no action against yeast and bacteria. Certain unsaturated fatty acids facilitate the antifungal property, whereas sterols, phospholipids and oleic acid act as antagonists. It produces morphological abnormalities in fungi including curling, bulging and empyting of hyphae. Thus, it mainly functions through its effects on the plasma membrane.

Reference

[1]. Biochim Biophys Acta Biomembr. 2019 Apr 1;1861(4):738-747. doi: 10.1016/j.bbamem.2019.01.003. Epub 2019 Jan 10.
Domain redistribution within ergosterol-containing model membranes in the presence of the antimicrobial compound fengycin.
Mantil E(1), Crippin T(1), Avis TJ(2).
Author information: (1)Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada. (2)Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada; Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada. Electronic address: .
The cyclic lipopeptide fengycin, produced by Bacillus subtilis, exhibits its antimicrobial capabilities by altering the integrity of the cell membrane of plant pathogens. Previous work has correlated fengycin activity with membrane characteristics, such as sterol content. This work focused on the influence of fengycin on supported lipid bilayers containing varying levels of ergosterol. Total internal reflection fluorescence (TIRF) microscopy was used to visualize and distinguish ordered (Lβ/Lo) and disordered (Lα/Ld) domains in the model membranes following exposure to low (50 μg) and high (500 μg) fengycin doses. Application of an initial low dose of fengycin to 0% and 3% ergosterol-containing bilayers resulted in redistribution of Lα/Lβ and Lo/Ld domains, respectively, which the bilayers compensated and corrected for over time. These membranes were unable to tolerate a second 50 μg dose or a single high fengycin dose. The 6% ergosterol bilayers were able to tolerate sequential low doses of fengycin. Exposure of these bilayers to the high fengycin dose caused a decrease in the number of Lo domains, albeit less than that seen in the 0% and 3% ergosterol bilayers. Bilayers containing 12% ergosterol, exhibited the least amount of change after fengycin exposure. These were the only bilayer to exhibit an increase in area taken up by ordered domains. These results suggest fengycin may preferentially act on the Lβ or Lo phase, the area in which ergosterol resides. Bilayers containing low levels of ergosterol appear to be more sensitive to the lipopeptide, suggesting ergosterol plays a role in buffering perturbations caused by fengycin.
DOI: 10.1016/j.bbamem.2019.01.003 PMID: 30639286 [Indexed for MEDLINE]

[2]. J Org Chem. 2018 Dec 21;83(24):15297-15311. doi: 10.1021/acs.joc.8b02553. Epub 2018 Dec 10.
Total Solid-Phase Synthesis of Dehydroxy Fengycin Derivatives.
Rosés C(1), Camó C(1), Oliveras À(1), Moll L(1), López N(1), Feliu L(1), Planas M(1).
Author information: (1)LIPPSO, Department of Chemistry , University of Girona , Maria Aurèlia Capmany 69 , 17003 Girona , Spain.
A rapid and efficient solid-phase strategy for the synthesis of dehydroxy fengycins derivatives is described. This synthetic approach involved the linkage of a Tyr to a Wang resin via a Mitsunobu reaction and the elongation of the peptide sequence followed by subsequent acylation of the N-terminus of the resulting linear peptidyl resin, esterification of the phenol group of a Tyr with an Ile, and final macrolactamization. The amino acid composition as well as the presence of the N-terminal acyl group significantly influenced the stability of the macrolactone. Cyclic lipodepsipeptides with a l-Tyr3/d-Tyr9 configuration were more stable than those containing the Tyr residues with an opposite configuration. This work constitutes the first approach on the total solid-phase synthesis of dehydroxy fengycin derivatives.
DOI: 10.1021/acs.joc.8b02553 PMID: 30525634

[3]. Curr Microbiol. 2020 Mar;77(3):443-451. doi: 10.1007/s00284-019-01855-w. Epub 2020 Jan 2.
Characterization of New Fengycin Cyclic Lipopeptide Variants Produced by Bacillus amyloliquefaciens (ET) Originating from a Salt Lake of Eastern Algeria.
Ait Kaki A(1)(2)(3), Smargiasso N(4), Ongena M(5), Kara Ali M(6), Moula N(7), De Pauw E(4), Kacem Chaouche N(6).
Author information: (1)Faculty of Sciences, Department of Biology, University of M'Hamed Bougara, 35000, Boumerdès, Algeria. . (2)Bioindustries Unit, Gembloux Agrobiotech, University of Liege, Passage of the Deportees 2, 5030, Gembloux, Belgium. . (3)Laboratory of Mycology, Biology and Biotechnology, Faculty of Natural and Life Sciences, Department of Applied Biology, University of Mentouri 1, 25000, Constantine, Algeria. . (4)Mass Spectrometry Laboratory, Molecular Systems Research Unit, University of Liege, B6C, B 400, Liege, Belgium. (5)Bioindustries Unit, Gembloux Agrobiotech, University of Liege, Passage of the Deportees 2, 5030, Gembloux, Belgium. (6)Laboratory of Mycology, Biology and Biotechnology, Faculty of Natural and Life Sciences, Department of Applied Biology, University of Mentouri 1, 25000, Constantine, Algeria. (7)Department of Animal Productions, Faculty of Veterinary Medicine, University of Liege, Colonster Boulevard 20, 4000, Liege, Belgium.
Fengycin antibiotic displays a strong antifungal activity and inhibits the growth of a wide range of plant pathogens especially filamentous fungi. The main objective of the present study is to characterize fengycin variants produced by B. amyloliquefaciens strain (ET). LC-MS analysis of fengycin extracts has shown several molecular ion peaks corresponding to conventional fengycin homologues (MH + : m/z 1463.9; 1491.9; 1506) and some new ones (MH + : m/z 1433; 1447; 1461; and 1477). Further characterization of these precursor ions was carried out by LC-MS.MS analysis. Reporter fragment ions were observed (named A and B), they correspond to the cleavage of Orn2-Tyr3 (A), Glu1-Orn2 (B), and used for identifying fengycin variants. The reporter fragment couple ions [A/B] at [m/z 966.5/1080.5] and [m/z 994.4 /1108.5] represent fengycin A and B, respectively. The diagnostic ions at ([m/z 980/1094]) may correspond to fengycin C3, D, S or B2. Interestingly, unknown diagnostic product ions at [m/z 951/1065] and [m/z 979/1093] were detected for the first time in this study which prove that they correspond to new fengycin variants, named fengycin X and fengycin Y, respectively. The fengycin X results from a substitution of the glutamine amino acid (Q), at position 8 of the fengycin A peptide part, by an isoleucine (I) or a leucine (L) residue. This mutation should be the same in fengycin Y but compared to fengycin B.
DOI: 10.1007/s00284-019-01855-w PMID: 31894376 [Indexed for MEDLINE]

[4]. Sci Rep. 2019 Nov 5;9(1):16034. doi: 10.1038/s41598-019-52551-5.
Fengycin induces ion channels in lipid bilayers mimicking target fungal cell membranes.
Zakharova AA(1), Efimova SS(2), Malev VV(1)(3), Ostroumova OS(1).
Author information: (1)Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, 194064, Russian Federation. (2)Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, 194064, Russian Federation. . (3)St. Petersburg State University, Petergof, 198504, Russian Federation.
The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 μM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range. FE channels were characterized by asymmetric conductance-voltage characteristic. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. The pore formation ability of FE was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels were characterized by weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile were used to modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane.
DOI: 10.1038/s41598-019-52551-5 PMCID: PMC6831686 PMID: 31690786 [Indexed for MEDLINE]

[5]. Microb Pathog. 2020 Dec;149:104509. doi: 10.1016/j.micpath.2020.104509. Epub 2020 Sep 19.
Antifungal evaluation of fengycin isoforms isolated from Bacillus amyloliquefaciens PPL against Fusarium oxysporum f. sp. lycopersici.
Kang BR(1), Park JS(2), Jung WJ(3).
Author information: (1)Institute of Environmentally-Friendly Agriculture, Chonnam National University, Gwangju, 61186, Republic of Korea. (2)International Analysis Institute, Naju, 58325, Republic of Korea. (3)Department of Agricultural Chemistry, Institute of Environmentally-Friendly Agriculture, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: .
Bacillus amyloliquefaciens PPL is known to have a broad spectrum antifungal activity against plant pathogenic fungi. We focused on the cyclic lipopeptides (CLPs) extracted from the culture broth that are known to promote the ability and the efficiency of B. amyloliquefaciens PPL to control fungal diseases in pepper and tomato. In this study, the PPL strain exhibited enhanced culture yield and increased production of fengycin lipopeptides upon lecithin supplementation. The purified iturin A fraction from strain PPL exhibited higher antifungal activity (73 – 80%) against pepper anthracnose than fengycin fraction in vitro and in vivo. However, the control of tomato Fusarium wilt by the PPL strain was mainly attributed to fengycin lipopeptides. A comparison of liquid chromatography-mass spectrometry (LC-MS) and LC-tandem MS analysis of the filtrate, we found that the antifungal compounds against Fusarium wilt present in the strain PPL culture filtrate were a series of isoforms of fengycin (type F1, F2, and F3). The purified fengycin F1 type showed better antifungal activity against Fusarium wilt compared the other isoforms. To the best of our knowledge, this is the first study to report the antifungal activity of fengycin isoform types in the context of Fusarium wilt. The CLPs produced by the PPL strain are potential candidates for controlling fungal disease in tomato and pepper plants.
DOI: 10.1016/j.micpath.2020.104509 PMID: 32956793