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Surfactin

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Surfactin
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.110.185 Edit this at Wikidata
  • 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:
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
TCDB1.D.11
OPM superfamily172
OPM protein2npv

Surfactin is a very powerful surfactant commonly used as an antibiotic. It is a bacterial cyclic lipopeptide, largely prominent for its exceptional surfactant power.[2] Its amphiphilic properties help this substance to survive in both hydrophilic and hydrophobic environments. It is an antibiotic produced by the Gram-positive endospore-forming bacteria Bacillus subtilis.[3] In the course of various studies of its properties, surfactin was found to exhibit effective characteristics like antibacterial, antiviral, antifungal, anti-mycoplasma and hemolytic activities.[4]

Structure and Synthesis

Surfactin's structure consists of a peptide loop of seven amino acids (L-aspartic acid, L-leucine, glutamic acid, L-leucine, L-valine and two D-leucines), and a hydrophobic fatty acid chain thirteen to fifteen carbons long which allows it to penetrate cellular membranes. Glutamic acid and aspartic acid residues at positions 1 and 5 respectively, constituting a minor polar domain. On the opposite side, valine residue at position 4 extends down facing the fatty acid chain, making up a major hydrophobic domain. Below critical micellar concentrations (CMCs) the fatty acid tail can extend freely into solution, and then participate in hydrophobic interactions within micelles.[5] This antibiotic is synthesized by a linear nonribosomal peptide synthetase, surfactin synthetase, and has, in solution, a characteristic "horse saddle" conformation that explains its large spectrum of biological activity.[6]

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 a concentration as low as 20 µM.[7] Surfactin accomplishes this effect as it occupies the intermolecular space between water molecules, decreasing the attractive forces between adjacent water molecules, mainly hydrogen bonds, creating a more fluid solution that can go into tighter regions of space increasing water’s wetting ability.[8] Overall, this property is significant not only for surfactin but for surfactants as a whole, as they are primarily used as detergents and soaps.

Molecular mechanisms

There are three prevailing hypotheses for how surfactin works.[9] These are described below.

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" of sorts which easily stabilizes divalent cations. Calcium ions make for the best-fitting cations stabilizing the surfactin conformation and functioning 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, with its headgroup in proximity to the phospholipids polar heads. Attachment of a cation to causes the complex to cross the bilipidic layer undergoing a flip-flop. The headgroup aligns itself with the phospholipids of the inner sheet and the fatty acid chain interacts with the phospholipids acyl chains.[10] The cation is then delivered into the intracellular medium.

Pore-forming effect

The pore-forming (ion channel) effect is characterized by the formation of cationic channels. It would require surfactin to self-associate inside the membrane, since it cannot span across the cellular membrane. Supramolecular-like structures by successive self-association could then form a channel. This hypothesis for the most part applies only to uncharged membranes where there is a minimal energy barrier between outer and inner membrane leaflets.[11]

Detergent effect

The detergent effect draws on surfactin's ability to insert its fatty acid chain into the bilipidic layer causing disorganization leading to membrane permeability.[12] 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.[13]

Biological properties

Surfactin has a nonspecific mode of action, which originates both benefits and disadvantages. It’s advantageous in the sense that surfactin can act on many kinds of cell membranes, both Gram-positive and Gram-negative. Its non-specificity also has bearing on its tendency to not produce resistant strains of bacteria. Consequently, this efficient mode of cell destruction is indiscriminate, and attacks red blood cells with deadly efficiency.

Antibacterial and antiviral properties

Surfactin, true to its antibiotic nature, has a very significant antibacterial property, as it is capable of penetrating the cell membranes of all types of bacteria. There are two main types of bacteria and they are Gram-negative and Gram-positive. The two bacteria types differ in the composition of their membrane. The Gram-negative bacteria have an outer lipopolysaccharide membrane and a thin peptidoglycan layer followed by a phospholipids bilayer, whereas the Gram-positive bacteria lack the outer membrane and carry a thicker peptidoglycan layer as well as a phospholipids bilayer.[14] This is an essential factor that contributes to surfactin’s detergent-like activity as it is able to create a permeable environment for the lipid bilayer and causes disruption that solubilizes the membrane.
For surfactin to carry out its antibacterial property successfully, the bacterium needs to be treated with a high concentration. In fact, surfactin needs to be in concentrations between 12–50 µg/ml in order for it to carry out minimal antibacterial effects.[15] This is also known as the minimum inhibitory concentration (MIC).
The antiviral effects of surfactin distinguish this antibiotic from others. This property is such because surfactin has been found to disintegrate enveloped viruses. Surfactin not only disintegrates the viral lipid enveloped, but also the capsid of the virus through ion channel formations. This process has been proven through test on several envelop viruses such as HIV and HSV.[16] Also, the isoforms of the fatty acid chain containing 14 or 15 carbon atoms exhibited an improvement in inactivation of the viral envelops. Unfortunately, surfactin only affected cell-free viruses and those that had penetrated the cell were unaffected. Concurrently, if surfactin were exposed to a high medium of protein or lipid concentrations, its antiviral activity would be limited. This is also known as the buffer effect and is a significant drawback in surfactin’s antiviral activity.

Toxicity

Surfactin has one major drawback: its non-specific cytotoxicity. This is seen as surfactin has the ability to lyse animal cells as well as pathogen cells. The hemolytic effect has been the result of surfactin having the ability to lyse red blood cells that is enough to warrant caution if used intravascularly. Fortunately, these results were seen at high concentrations of about 40 µM to 60 µM. These concentrations also exhibited the effect of proliferating cells in vitro though it also was the LD50 for this type of cells. At concentrations below 25 µM, toxicity effects of surfactin are not significant[citation needed].

References

  1. ^ Ishigami, Yutaka; Osman, Mohamad; Nakahara, Hisae; Sano, Yoh; Ishiguro, Ryo; Matsumoto, Mutsuo (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. Recent trends in the biochemistry of Surfactin; Applied Microbiol Biotechnol. (1999) 51:553–63
  4. ^ Pooja Singh and Swaranjit Singh Cameotra; Potential applications of microbial surfactants in biomedical sciences; Institute of Microbial Technology, Sector 39 A, Chandigarh 160036, India.
  5. ^ Grau, A, J C. Gomez Fernandez, and R Peypoux. A Study on the Interactions of Surfactin With Phospholipid Vesicles. BBA (1999) 1418: 307–319.
  6. ^ Nathalie Hue, Laurent Serani, Olivier Laprévote; Structural investigation of cyclic peptidolipids from Bacillus subtilis by high-energy tandem mass spectrometry; Institut de Chimie des Substances Naturelles, CNRS, avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
  7. ^ Yeh MS, Wei YH, Chang JS. Enhanced Production of surfactin from Bacillus subtilis by addition of solid carriers (2005) Biotechnol Prog. 4:1329–34
  8. ^ Dufour S, Deleu M, Nott K, Wathelet B, Thonart P, Paquot M. Hemolytic activity of new linear surfactin analogs in relation to their physico-chemical properties. (2005) BBAGEN 25949:1–9
  9. ^ Deleu, M, O Bouffioux, H Razafindralambo, and M Paquot. Interaction of Surfactin with Membranes: A Computational Approach. (2003) Langmuir 19: 3377–3385.
  10. ^ Heerklotz, H, T Wieprecht, and J Seelig. Membrane Perturbation oby the Lipopeptide Surfactin and Detergents as Studied by Deuterium NMR. J. Phys. Chem. (2004)108: 4909–4915
  11. ^ Deleu, M, O Bouffioux, H Razafindralambo, and M Paquot. Interaction of Surfactin with Membranes: A Computational Approach. (2003) Langmuir 19: 3377–3385.
  12. ^ 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.
  13. ^ Maire, M, P Champeil, and J V. Moller. Interaction of Membrane Proteins and lipids with Solubilizing Detergents. BBA (2000) 1508: 86–111.
  14. ^ Bergey, John G. Holt, Noel R. Krieg, Peter H.A. Sneath (1994). Bergey's Manual of Determinative Bacteriology, 9th ed., Lippincott Williams & Wilkins. ISBN 0-683-00603-7.
  15. ^ Heerklotz H, Seelig J. Detergent-like action of the antibiotic peptide surfactin on lipid membranes. (2001) Biophysical J 81(3):1547–54
  16. ^ Jung M, Lee S, Kim H, Kim H. Recent Studies on Natural Products as Anti-HIV Agents. (2000). Current Medicinal Chemistry 7:000-000
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