Surfactin
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| Identifiers | |
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3D model (JSmol)
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.110.185 |
PubChemCID
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CompTox Dashboard(EPA)
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| Properties | |
| C53H93N7O13 | |
| Molar mass | 1036.3 g/mol |
| Surface tension: | |
| 9.4 × 10−6M (pH 8.7)[1] | |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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| Identifiers | |
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| Symbol | N/A |
| TCDB | 1.D.11 |
| OPM superfamily | 163 |
| OPM protein | 2npv |
Surfactinis a cycliclipopeptide,commonly used as anantibioticfor its capacity as asurfactant.[2]It is anamphiphilecapable of withstandinghydrophilicandhydrophobicenvironments. TheGram-positive bacterialspeciesBacillus subtilisproduces surfactin for its antibiotic effects against competitors.[3]Surfactin showcasesantibacterial,antiviral,antifungal,andhemolyticeffects.[4]
Structure and Synthesis
[edit]The structure consists of apeptideloop of sevenamino acids(L-glutamic acid,L-leucine,D-leucine,L-valine,L-aspartic acid,D-leucine, and L-leucine) and a β-hydroxyfatty acidof variable length, thirteen to fifteencarbonatoms long.[5]The glutamic acid and aspartic acid residues give the ring its hydrophilic character, as well as its negative charge. Conversely, the valine residue extends down, facing the fatty acid chain, to form a major hydrophobic domain. Below criticalmicellarconcentrations (CMCs), the fatty acid tail can extend freely intosolution,participating in hydrophobic interactions withinmicelles.[6]This antibiotic is synthesized by a linearnonribosomal peptide synthetase,surfactin synthetase (Q04747). In solution, it has a characteristic "horse saddle"conformation(PDB:2NPV) that explains its large spectrum of biological activity.[7][8]
Physical properties
[edit]Surface tension
[edit]Surfactin, like other surfactants, affects the surface tension of liquids in which it is dissolved. It can lower thewater'ssurface tensionfrom 72 mN/m to 27 mN/m at concentrations as low as 20 μM.[9]Surfactin accomplishes this effect by occupying the intermolecular space between watermolecules,decreasing the attractive forces between adjacent water molecules, mainlyhydrogen bonds,to increase the solution's fluidity. This property makes surfactin and other surfactants useful as detergents andsoaps.[10]
Molecular mechanisms
[edit]There are three prevailinghypothesesfor how surfactin works.[11]
Cation-carrier effect
[edit]The cation-carrier effect is characterized by surfactin's ability to drivemonovalentanddivalentcations through anorganicbarrier. The twoacidicresidues aspartate and glutamate form a "claw" to stabilize divalentcations,such asCa2+ions used as an assembly template for the formation ofmicelles.When surfactin penetrates the outer sheet, its fatty acid chain interacts with theacylchains of thephospholipids,orienting its headgroup toward the phospholipids' polar heads. Attachment of a cation causes the complex to cross the bilipidic layer usingflippaseenzymes. The headgroup aligns itself with the phospholipids of the inner sheet and the fatty acid chain interacts with the phospholipids acyl chains. The cation is then delivered into the intracellular medium.[12]
Pore-forming effect
[edit]The pore-forming (ion channel) effect is characterized by the formation of cationic channels. It requires surfactin to self-associate inside the membrane since it cannot span across the cellular membrane. Under a hypothesis focused on uncharged membranes with minimalactivation energyrequired to cross between inner and outer leaflets,molecular self-assemblywould form a channel structure.[11]
Detergent effect
[edit]The detergent effect draws on surfactin's ability to insert its fatty acid chain into the phospholipid layer, disorganizing the cell membrane to increase its permeability.[13]Insertion of several surfactin molecules into the membrane can lead to the formation of mixed micelles by self-association and bilayer influenced by fatty chain hydrophobicity ultimately leading to bilayer solubilization.[14]
Biological properties
[edit]Antibacterial and antiviral properties
[edit]Surfactin is abroad-spectrum antibioticwith detergent-like activity increasing the permeability of cell membranes in all bacteria, regardless of theirGram stainclassification.[15]The minimum inhibitory concentration (MIC) of surfactin is between 12-50 μg/ml.[16]
Surfactin is also capable of degradingviral envelopelipids and forming ion channels in the innercapsidwith experimental evidence showing inhibition ofHIVandHSV.However, surfactin can only degrade viruses when they are outside of host cells. Furthermore, when the environment is packed with proteins and lipids, surfactin faces a buffer effect lowering its antiviral activity.[17]
Toxicity
[edit]Surfactin has non-specific cytotoxicity, causinglysisthrough disruption to the phospholipid bilayer present in all cells. When injected into humans as an intravascular antibiotic at concentrations at or above theLD50of 40-80 μM, surfactin has hemolytic effects.[18]
See also
[edit]References
[edit]- ^Ishigami Y, Osman M, Nakahara H, Sano Y, Ishiguro R, Matsumoto M (July 1995). "Significance of β-sheet formation for micellization and surface adsorption of surfactin".Colloids and Surfaces B: Biointerfaces.4(6): 341–348.doi:10.1016/0927-7765(94)01183-6.
- ^Mor, A. Peptide-based antibiotics: A potential answer to raging antimicrobial resistance.Drug Develop. Res. (2000) 50:440–447.
- ^Peypoux F, Bonmatin JM, Wallach J (May 1999). "Recent trends in the biochemistry of surfactin".Applied Microbiology and Biotechnology.51(5): 553–63.doi:10.1007/s002530051432.PMID10390813.S2CID35677695.
- ^Singh P, Cameotra SS (March 2004). "Potential applications of microbial surfactants in biomedical sciences".Trends in Biotechnology.22(3): 142–6.doi:10.1016/j.tibtech.2004.01.010.PMID15036865.
- ^Bonmatin JM, Laprévote O, Peypoux F (September 2003)."Diversity among microbial cyclic lipopeptides: iturins and surfactins. Activity-structure relationships to design new bioactive agents".Combinatorial Chemistry & High Throughput Screening.6(6): 541–56.doi:10.2174/138620703106298716.PMID14529379.
- ^Grau A, Gómez Fernández JC, Peypoux F, Ortiz A (May 1999)."A study on the interactions of surfactin with phospholipid vesicles".Biochimica et Biophysica Acta (BBA) - Biomembranes.1418(2): 307–19.doi:10.1016/S0005-2736(99)00039-5.PMID10320682.
- ^Hue N, Serani L, Laprévote O (2001). "Structural investigation of cyclic peptidolipids from Bacillus subtilis by high-energy tandem mass spectrometry".Rapid Communications in Mass Spectrometry.15(3): 203–9.Bibcode:2001RCMS...15..203H.doi:10.1002/1097-0231(20010215)15:3<203::AID-RCM212>3.0.CO;2-6.PMID11180551.
- ^Tsan P, Volpon L, Besson F, Lancelin JM (February 2007). "Structure and dynamics of surfactin studied by NMR in micellar media".Journal of the American Chemical Society.129(7): 1968–77.doi:10.1021/ja066117q.PMID17256853.
- ^Yeh MS, Wei YH, Chang JS (2005). "Enhanced production of surfactin from Bacillus subtilis by addition of solid carriers".Biotechnology Progress.21(4): 1329–34.doi:10.1021/bp050040c.PMID16080719.S2CID20942103.
- ^Wójtowicz K, Czogalla A, Trombik T, Łukaszewicz M (2021-12-01)."Surfactin cyclic lipopeptides change the plasma membrane composition and lateral organization in mammalian cells".Biochimica et Biophysica Acta (BBA) - Biomembranes.1863(12): 183730.doi:10.1016/j.bbamem.2021.183730.ISSN0005-2736.PMID34419486.
- ^abDeleu M, Bouffioux O, Razafindralambo H, Paquot M, Hbid C, Thonart P, Jacques P, Brasseur R (April 2003)."Interaction of Surfactin with Membranes: A Computational Approach"(PDF).Langmuir.19(8): 3377–3385.doi:10.1021/la026543z.
- ^Heerklotz H, Wieprecht T, Seelig J (April 2004). "Membrane Perturbation by the Lipopeptide Surfactin and Detergents as Studied by Deuterium NMR".The Journal of Physical Chemistry B.108(15): 4909–4915.doi:10.1021/jp0371938.
- ^Kragh-Hansen, U, M Maire, and J Moller. The Mechanism of Detergent Solubilization of Liposomes and Protein-Containing Membranes.Biophys. J. (1998) 75:2932–2946.
- ^le Maire M, Champeil P, Moller JV (November 2000)."Interaction of membrane proteins and lipids with solubilizing detergents".Biochimica et Biophysica Acta (BBA) - Biomembranes.1508(1–2): 86–111.doi:10.1016/S0304-4157(00)00010-1.PMID11090820.
- ^Sudarmono P, Wibisana A, Listriyani LW, Sungkar S (2019-03-10)."Characterization and Synergistic Antimicrobial Evaluation of Lipopeptides from Bacillus amyloliquefaciens Isolated from Oil-Contaminated Soil".International Journal of Microbiology.2019:e3704198.doi:10.1155/2019/3704198.ISSN1687-918X.PMC6431436.PMID30956662.
- ^Heerklotz H, Seelig J (September 2001)."Detergent-like action of the antibiotic peptide surfactin on lipid membranes".Biophysical Journal.81(3): 1547–54.Bibcode:2001BpJ....81.1547H.doi:10.1016/S0006-3495(01)75808-0.PMC1301632.PMID11509367.
- ^Jung M, Lee S, Kim H (June 2000). "Recent studies on natural products as anti-HIV agents".Current Medicinal Chemistry.7(6): 649–61.doi:10.2174/0929867003374822.PMID10702631.
- ^Dehghan-Noudeh G, Housaindokht M, Sedigeh Fazly Bazzar B (June 2005)."Isolation, Characterization, and Investigation of Surface and Hemolytic Activities of a Lipopeptide Biosurfactant Produced by Bacillus subtilis ATCC 6633".The Journal of Microbiology.43(3). The Microbiological Society of Korea: 272–276.PMID15995646.