Surfactin

Last updated
Surfactin
Surfactin.png
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.110.185 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
  • InChI=1S/C53H93N7O13/c1-30(2)20-18-16-14-13-15-17-19-21-36-28-43(61)54-37(22-23-44(62)63)47(66)55-38(24-31(3)4)48(67)57-40(26-33(7)8)51(70)60-46(35(11)12)52(71)58-41(29-45(64)65)50(69)56-39(25-32(5)6)49(68)59-42(27-34(9)10)53(72)73-36/h30-42,46H,13-29H2,1-12H3,(H,54,61)(H,55,66)(H,56,69)(H,57,67)(H,58,71)(H,59,68)(H,60,70)(H,62,63)(H,64,65)/t36-,37+,38+,39-,40-,41+,42+,46+/m1/s1
    Key: NJGWOFRZMQRKHT-WGVNQGGSSA-N
  • InChI=1/C53H93N7O13/c1-30(2)20-18-16-14-13-15-17-19-21-36-28-43(61)54-37(22-23-44(62)63)47(66)55-38(24-31(3)4)48(67)57-40(26-33(7)8)51(70)60-46(35(11)12)52(71)58-41(29-45(64)65)50(69)56-39(25-32(5)6)49(68)59-42(27-34(9)10)53(72)73-36/h30-42,46H,13-29H2,1-12H3,(H,54,61)(H,55,66)(H,56,69)(H,57,67)(H,58,71)(H,59,68)(H,60,70)(H,62,63)(H,64,65)/t36-,37+,38+,39-,40-,41+,42+,46+/m1/s1
    Key: NJGWOFRZMQRKHT-WGVNQGGSBQ
  • CC(C)CCCCCCCCC[C@@H]1CC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)O1
Properties
C53H93N7O13
Molar mass 1036.3 g/mol
Surface tension:
CMC
9.4 × 10−6 M (pH 8.7) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Identifiers
SymbolN/A
TCDB 1.D.11
OPM superfamily 163
OPM protein 2npv

Surfactin is a cyclic lipopeptide, commonly used as an antibiotic for its capacity as a surfactant. [2] It is an amphiphile capable of withstanding hydrophilic and hydrophobic environments. The Gram-positive bacterial species Bacillus subtilis produces surfactin for its antibiotic effects against competitors. [3] Surfactin showcases antibacterial, antiviral, antifungal, and hemolytic effects. [4]

Contents

Structure and Synthesis

The structure consists of a peptide loop of seven amino acids (L-glutamic acid, L-leucine, D-leucine, L-valine, L-aspartic acid, D-leucine, and L-leucine) and a β-hydroxy fatty acid of variable length, thirteen to fifteen carbon atoms 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 critical micellar concentrations (CMCs), the fatty acid tail can extend freely into solution, participating in hydrophobic interactions within micelles. [6] This antibiotic is synthesized by a linear nonribosomal 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

Surface tension

Surfactin, like other surfactants, affects the surface tension of liquids in which it is dissolved. It can lower the water's surface tension from 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 water molecules, decreasing the attractive forces between adjacent water molecules, mainly hydrogen bonds, to increase the solution's fluidity. This property makes surfactin and other surfactants useful as detergents and soaps. [10]

Molecular mechanisms

There are three prevailing hypotheses for how surfactin works. [11]

Cation-carrier effect

The cation-carrier effect is characterized by surfactin's ability to drive monovalent and divalent cations through an organic barrier. The two acidic residues aspartate and glutamate form a "claw" to stabilize divalent cations, such as Ca2+ ions used as an assembly template for the formation of micelles. When surfactin penetrates the outer sheet, its fatty acid chain interacts with the acyl chains of the phospholipids, orienting its headgroup toward the phospholipids' polar heads. Attachment of a cation causes the complex to cross the bilipidic layer using flippase enzymes. 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

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 minimal activation energy required to cross between inner and outer leaflets, molecular self-assembly would form a channel structure. [11]

Detergent effect

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

Antibacterial and antiviral properties

Surfactin is a broad-spectrum antibiotic with detergent-like activity increasing the permeability of cell membranes in all bacteria, regardless of their Gram stain classification. [15] The minimum inhibitory concentration (MIC) of surfactin is between 12-50 μg/ml. [16]

Surfactin is also capable of degrading viral envelope lipids and forming ion channels in the inner capsid with experimental evidence showing inhibition of HIV and HSV. 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

Surfactin has non-specific cytotoxicity, causing lysis through disruption to the phospholipid bilayer present in all cells. When injected into humans as an intravascular antibiotic at concentrations at or above the LD50 of 40-80 μM, surfactin has hemolytic effects. [18]

Related Research Articles

<span class="mw-page-title-main">Phospholipid</span> Class of lipids

Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue. Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine.

<span class="mw-page-title-main">Detergent</span> Surfactants with cleansing properties

A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are more soluble in hard water, because the polar sulfonate is less likely than the polar carboxylate to bind to calcium and other ions found in hard water.

<span class="mw-page-title-main">Surfactant</span> Substance that lowers the surface tension between a liquid and another material

Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word "surfactant" is a blend of surface-active agent, coined c. 1950. As they consist of a water-repellent and a water-attracting part, they enable water and oil to mix; they can form foam and facilitate the detachment of dirt.

<span class="mw-page-title-main">Transmembrane protein</span> Protein spanning across a biological membrane

A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents.

<span class="mw-page-title-main">Peripheral membrane protein</span> Membrane proteins that adhere temporarily to membranes with which they are associated

Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.

<span class="mw-page-title-main">Micelle</span> Group of fatty molecules suspended in liquid by soaps and/or detergents

A micelle or micella is an aggregate of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension. A typical micelle in water forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle centre.

<i>n</i>-Octyl β-<small>D</small>-thioglucopyranoside Chemical compound

n-Octyl β-d-thioglucopyranoside is a mild nonionic detergent that is used for cell lysis or to solubilise membrane proteins without denaturing them. This is particularly of use in order to crystallise them or to reconstitute them into lipid bilayers. It has a critical micelle concentration of 9 mM.

Lipophilicity is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are called lipophilic. Such non-polar solvents are themselves lipophilic, and the adage "like dissolves like" generally holds true. Thus lipophilic substances tend to dissolve in other lipophilic substances, whereas hydrophilic ("water-loving") substances tend to dissolve in water and other hydrophilic substances.

<span class="mw-page-title-main">Antimicrobial peptides</span> Class of peptides that have antimicrobial activity

Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent, broad spectrum antimicrobials which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria, enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes, can form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators.

<span class="mw-page-title-main">Amphiphile</span> Hydrophilic and lipophilic chemical compound

An amphiphile, or amphipath, is a chemical compound possessing both hydrophilic and lipophilic (fat-loving) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic compounds include surfactants. The phospholipid amphiphiles are the major structural component of cell membranes.

<span class="mw-page-title-main">Dipalmitoylphosphatidylcholine</span> Chemical compound

Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group.

<span class="mw-page-title-main">Tyrocidine</span> Chemical compound

Tyrocidine is a mixture of cyclic decapeptides produced by the bacteria Brevibacillus brevis found in soil. It can be composed of 4 different amino acid sequences, giving tyrocidine A–D. Tyrocidine is the major constituent of tyrothricin, which also contains gramicidin. Tyrocidine was the first commercially available antibiotic, but has been found to be toxic toward human blood and reproductive cells. The function of tyrocidine within its host B. brevis is thought to be regulation of sporulation.

<span class="mw-page-title-main">Lipid polymorphism</span>

Polymorphism in biophysics is the ability of lipids to aggregate in a variety of ways, giving rise to structures of different shapes, known as "phases". This can be in the form of spheres of lipid molecules (micelles), pairs of layers that face one another, a tubular arrangement (hexagonal), or various cubic phases. More complicated aggregations have also been observed, such as rhombohedral, tetragonal and orthorhombic phases.

A lipopeptide is a molecule consisting of a lipid connected to a peptide. They are able to self-assemble into different structures. Many bacteria produce these molecules as a part of their metabolism, especially those of the genus Bacillus, Pseudomonas and Streptomyces. Certain lipopeptides are used as antibiotics. Due to the structural and molecular properties such as the fatty acid chain, it poses the effect of weakening the cell function or destroying the cell. Other lipopeptides are toll-like receptor agonists. Certain lipopeptides can have strong antifungal and hemolytic activities. It has been demonstrated that their activity is generally linked to interactions with the plasma membrane, and sterol components of the plasma membrane could play a major role in this interaction. It is a general trend that adding a lipid group of a certain length to a lipopeptide will increase its bactericidal activity. Lipopeptides with a higher amount of carbon atoms, for example 14 or 16, in its lipid tail will typically have antibacterial activity as well as anti-fungal activity. Therefore, an increase in the alkyl chain can make lipopeptides soluble in water. As well, it opens the cell membrane of the bacteria, so antimicrobial activity can take place.

<span class="mw-page-title-main">Nanodisc</span> Synthetic model membrane system

A nanodisc is a synthetic model membrane system which assists in the study of membrane proteins. Nanodiscs are discoidal proteins in which a lipid bilayer is surrounded by molecules that are amphipathic molecules including proteins, peptides, and synthetic polymers. It is composed of a lipid bilayer of phospholipids with the hydrophobic edge screened by two amphipathic proteins. These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation. Nanodiscs are structurally very similar to discoidal high-density lipoproteins (HDL) and the MSPs are modified versions of apolipoprotein A1 (apoA1), the main constituent in HDL. Nanodiscs are useful in the study of membrane proteins because they can solubilise and stabilise membrane proteins and represent a more native environment than liposomes, detergent micelles, bicelles and amphipols.

A model lipid bilayer is any bilayer assembled in vitro, as opposed to the bilayer of natural cell membranes or covering various sub-cellular structures like the nucleus. They are used to study the fundamental properties of biological membranes in a simplified and well-controlled environment, and increasingly in bottom-up synthetic biology for the construction of artificial cells. A model bilayer can be made with either synthetic or natural lipids. The simplest model systems contain only a single pure synthetic lipid. More physiologically relevant model bilayers can be made with mixtures of several synthetic or natural lipids.

<span class="mw-page-title-main">Ethanol-induced non-lamellar phases in phospholipids</span>

The presence of ethanol can lead to the formations of non-lamellar phases also known as non-bilayer phases. Ethanol has been recognized as being an excellent solvent in an aqueous solution for inducing non-lamellar phases in phospholipids. The formation of non-lamellar phases in phospholipids is not completely understood, but it is significant that this amphiphilic molecule is capable of doing so. The formation of non-lamellar phases is significant in biomedical studies which include drug delivery, the transport of polar and non-polar ions using solvents capable of penetrating the biomembrane, increasing the elasticity of the biomembrane when it is being disrupted by unwanted substances and functioning as a channel or transporter of biomaterial.

<span class="mw-page-title-main">Cell membrane</span> Biological membrane that separates the interior of a cell from its outside environment

The cell membrane is a biological membrane that separates and protects the interior of a cell from the outside environment. The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of a cell, being selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity, and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall and the carbohydrate layer called the glycocalyx, as well as the intracellular network of protein fibers called the cytoskeleton. In the field of synthetic biology, cell membranes can be artificially reassembled.

<span class="mw-page-title-main">Mycosubtilin</span> Chemical compound

Mycosubtilin is a natural lipopeptide with antifungal and hemolytic activities and isolated from Bacillus species. It belongs to the iturin lipopeptide family.

A proteolipid is a protein covalently linked to lipid molecules, which can be fatty acids, isoprenoids or sterols. The process of such a linkage is known as protein lipidation, and falls into the wider category of acylation and post-translational modification. Proteolipids are abundant in brain tissue, and are also present in many other animal and plant tissues. They include ghrelin, a peptide hormone associated with feeding. Many proteolipids are composed of proteins covalenently bound to fatty acid chains, often granting them an interface for interacting with biological membranes. They are not to be confused with lipoproteins, a kind of spherical assembly made up of many molecules of lipids and some apolipoproteins.

References

  1. ↑ 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.
  2. ↑ Mor, A. Peptide-based antibiotics: A potential answer to raging antimicrobial resistance. Drug Develop. Res. (2000) 50: 440–447.
  3. ↑ 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. PMID   10390813. S2CID   35677695.
  4. ↑ 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. PMID   15036865.
  5. ↑ 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. PMID   14529379.
  6. ↑ 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 . PMID   10320682.
  7. ↑ 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. PMID   11180551.
  8. ↑ 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. PMID   17256853.
  9. ↑ 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. PMID   16080719. S2CID   20942103.
  10. ↑ 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 . ISSN   0005-2736. PMID   34419486.
  11. 1 2 Deleu 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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 . PMID   11090820.
  15. ↑ 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 . ISSN   1687-918X. PMC   6431436 . PMID   30956662.
  16. ↑ 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. PMC   1301632 . PMID   11509367.
  17. ↑ 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. PMID   10702631.
  18. ↑ 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. PMID   15995646.
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