Viscosin group

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The viscosin group owes its name to the cyclic lipopeptide viscosin, the first member of this group described in 1951, making it one of the first CLiPs described. (Groupé, 1951) Other members of the viscosin group include WLIP (Mortishire-Smith, 1991), short for the White Line Inducing Principle, the massetolides (Gerard, 1997), the viscosinamides (Nielsen, 1999, Geudens, 2014), the pseudodesmins (Sinnaeve, 2009), and the pseudophomins (Quail, 2002).  Viscosin and members have repeatedly been reported from a variety of Pseudomonas sources, indicating a prominent role in bacterial metabolism. Biological activities are abundant, including antibacterial, antifungal, antiviral, insecticidal activities, etc. (Geudens, 2018) The solid phase peptide synthesis of viscosin itself was described in 1989 (Burke, 1989), followed by a more efficient and automated solid phase peptide synthesis for other viscosin group members. (De Vleeschouwer, 2015, De Vleeschouwer, 2016)

The group features CLiPs with a nonapeptide chain, cyclized via an ester bond between the C-terminal carbonyl and the side chain of D-aThr3. At the N-terminal they are linked to a 3-hydroxy fatty, in most cases a 3R-hydroxydecanoic acid. Structural variations that occur within the viscosin group can be the presence of either a D-Glu2 or a D-Gln2; allowing a subdivision of the viscosin group in E- and Q-subgroups. A second type of variation that occurs is the presence of either an L- or D-configuration for Leu5, again allowing us to subdivide the viscosin group in two: the L- and D-subgroups. This creates a grid of four possible combinations: E/L, E/D, Q/L and Q/D; and a CLP has been described for each in the literature (viscosin, WLIP, viscosinamide A and pseudodesmin A; respectively). Finally, variations in hydrophobic amino acids can also occur at specific locations, most likely due to substrate flexibility of the adenylation domains.

Schematic representation of the viscosin group CLiPs

Structurally, CLiPs of the viscosin group form a short left-handed helix composed of L-Leu1 to D-Ser6, followed by a loop that brings the C-terminus in a suitable position for cyclization with D-aThr3. Overall, the structure is amphipathic, whereby the polar side-chains are separated from the hydrophobic ones. Overall, it can be concluded that the D/L stereoinversion within the viscosin group does not have a drastic impact on the molecular conformation or the general physicochemical behaviour. More specifically, it was found that the overall peptide fold remains the same while the surface distribution of the hydrophobic side chains, and thus amphipathicity, is (slightly) affected. (Geudens, 2014)

References

Burke, et al. “Preperative reversed-phase high-performance liquid chromatography in the synthesis of viscosin, a cyclic depsipeptide.” Journal of Chromatography484 (1989).

De Vleeschouwer. “Exploration of the structure-activity relationship of the cyclic lipopeptide pseudodesmin A enabled by an effective and versatile synthesis route.” Universiteit Gent, 2015.

De Vleeschouwer, et al. “First total synthesis of WLIP: on the importance of correct protecting group choice.” Journal of Peptide Science22, 3 (2016): https://dx.doi.org/10.1002/psc.2852.

Gerard, et al. “Massetolides A-H, antimycobacterial cyclic depsipeptides produced by two Pseumonads isolated from marine habitats.” Journal of Natural Products60 (1997).

Geudens, et al. “Impact of a stereocentre inversion in cyclic lipodepsipeptides from the viscosin group: a comparative study of the viscosinamide and pseudodesmin conformation and self-assembly.” ChemBioChem15, 18 (2014): https://dx.doi.org/10.1002/cbic.201402389.

Geudens, et al. “Cyclic lipodepsipeptides from Pseudomonas spp. – Biological Swiss-Army Knives.” Frontiers in Microbiology9, 1867 (2018): https://dx.doi.org/10.3389/fmicb.2018.01867.

Groupé, et al. “Observations on antiviral activity of viscosin.” Experimental Biology and Medicine78, 1 (1951).

Mortishire-Smith, et al. “Determination of the structure of an extracellular peptide produced by the mushroom Saprotroph Pseudomonas reactans.” Tetrahedron47, 22 (1991): https://dx.doi.org/10.1016/s0040-4020(01)80877-2.

Nielsen, et al. “Viscosinamide, a new cyclic depsipeptide with surfactant and antifungal properties produced by Pseudomonas fluorescens DR54.” Journal of Applied Microbiology86 (1999).

Quail, et al. “Pseudophomins A and B, a class of cyclic lipodepsipeptides isolated from a Pseudomonas species.” Acta Crystallographica Section C58, 5 (2002).

Sinnaeve, et al. “Structure and X-ray conformation of pseudodesmins A and B, two new cyclic lipodepsipeptides from Pseudomonas bacteria.” Tetrahedron65, 21 (2009): https://dx.doi.org/10.1016/j.tet.2009.03.045.

 

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