Amphisin

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Introduction

Amphisin is a cyclic lipodepsipeptide produced by non-ribosomal peptide synthetases in Pseudomonas species. It is the name-sake CLiP of a group of structurally similar lipopeptides, the Amphisin group. This group also contains arthrofactin (), lokisin (), tensin (), anikasin, milkisin () and the stechlisins ().

Original publicationSorensen, 2001
Original sourcePseudomonas sp. DSS73
Sequence determined byX-ray crystallography
Stereochemistry determined byX-ray crystallography
Other known sources (non-putative)n.a.

Chemical properties

Molecular formulaC66H114N12O20
Mono-isotopic mass1394.8272 Da (isobaric to other CLiPs, see text)
Molecular weight1395.7 g mol-1
SolubilitySoluble in MeOH, DMSO, DMF, buffer. Not soluble in acetonitrile, milliQ
CMC0.075 mM (Groboillot, 2011)
NMR data available in literaturen.a.

Chemical structure

Amphisin is a cyclic lipodepsipeptide (CLiP) produced by Pseudomonas sp. DSS73, isolated from the rhizosphere of sugar beet seedlings. (Sorensen, 2001) It consists of a undecapeptide sequence, linked to at a 3R-hydroxydecanoic acid (3-OH C10:0) moiety at the N-terminus, as determined by X-ray crystallography. At the C-terminal end, the peptide features an ester bond to the side chain of threonine at position 4, forming a macrocycle containing 9 of the 11 amino acid. The primary structure of amphisin is 3R-hydroxydecanoyl – D-Leu1- D-Asp2 – D-aThr3 – D-Leu4 – D-Leu5 – D-Ser6 – L-Leu7 – D-Gln8 – L-Leu9 – L-Ile10 – L-Asp11.

Chemical structure of amphisin
Schematic sequence of orfamide B, where shapes indicate amino acid configuration (circles = L-AA, squares = D-AA) and colors indicate amino acid polarity (green = hydrophobic, red = polar)

Biological activity

Amphisin is able to inhibit growth of fungi (Pythium ultimum and Rhizoctonia solani) (Nielsen, 2002, Andersen, 2003). No information is available on its antagonistic activities against other microorganisms.

Physicochemical properties

Most of the CLPs produced by Pseudomonas species are able to reduce the surface tension of growth media to different extents. In this respect, amphisin reduces the surface tension of water from 75 mN.m-1 to ~27 mN.m-1 (Nielsen, 2002). Moreover, the CLiP has also been investigated in soil remediation e.g. for the. removal of PAKs. (Groboillot, 2011, Portet-Koltalo, 2013)

Three-dimensional structure

The three-dimensional structure of amphisin was determined by X-ray crystallography. Similar to other Pseudomonas CLiPs, amphisin features a left-handed α-helix ranging between D-Leu1 and D-Ser6. The helix is followed by a so-called loop, a rigid structure without defined secondary structure that allows to fold the C-terminal end back to the middle of the helix, where cyclization occurs. Consequently, part of the helix is exocyclic, while part of it is contained within the macrocycle. Furthermore, the conformation is such that there is a clear separation between the polar and hydrophobic residues. This leads to the presence of both a hydrophobic and hydrophilic side on the molecular surface, leading to an amphipathic molecule, in agreement with its function of a biosurfactant.

X-ray structure of amphisin showing the presence of an N-terminal helix ranging from D-Leu1 to D-Ser6, followed by a rigid structure element (“loop”) that brings the C-terminal carbonyl in position to form the ester bond with the side chain of D-alloThr3.

References

Andersen, et al. “Surface motility in Pseudomonas sp. DSS73 is required for efficient biological containment of the root-pathogenic microfungi Rhizoctonia solani and Pythium ultimum.” Microbiology149, Pt 1 (2003): https://dx.doi.org/10.1099/mic.0.25859-0.

Götze, et al. “Structure, biosynthesis, and biological activity of the cyclic lipopeptide anikasin.” ACS Chemical Biology12, 10 (2017): https://dx.doi.org/10.1021/acschembio.7b00589.

Groboillot, et al. “Novel application of cyclolipopeptide amphisin: Feasibility study as additive to remediate polycyclic aromatic hydrocarbon (PAH) contaminated sediments.” International Journal of Molecular Sciences12, 3 (2011): https://dx.doi.org/10.3390/ijms12031787.

Hendriksen, et al. “Cyclic lipoundecapeptide tensin from Pseudomonas fluorescens strain 96.578.” Acta Crystallographica Section CC56 (2000).

Lange, et al. “Predicting the structure of cyclic lipopeptides by bioinformatics: structure revision of arthrofactin.” ChemBioChem13, 18 (2012): https://dx.doi.org/10.1002/cbic.201200532.

Marner, et al. “Molecular Networking-Guided Discovery and Characterization of Stechlisins, a Group of Cyclic Lipopeptides from a Pseudomonas sp.” J Nat Prod83, 9 (2020): https://dx.doi.org/10.1021/acs.jnatprod.0c00263.

Nielsen, et al. “Antibiotic and biosurfactant properties of cyclic lipopeptides produced by fluorescent Pseudomonas spp. from the sugar beet rhizosphere.” Applied and Environmental Microbiology68, 7 (2002): https://dx.doi.org/10.1128/aem.68.7.3416-3423.2002.

Portet-Koltalo, et al. “Investigation of the release of PAHs from artificially contaminated sediments using cyclolipopeptidic biosurfactants.” Journal of Hazardous Materials261 (2013): https://dx.doi.org/10.1016/j.jhazmat.2013.07.062.

Schlusselhuber, et al. “Characterization of milkisin, a novel lipopeptide with antimicrobial properties produced by Pseudomonas sp. UCMA 17988 isolated from bovine raw milk.” Frontiers in Microbiology9, 1030 (2018): https://dx.doi.org/10.3389/fmicb.2018.01030.

Sorensen, et al. “Cyclic lipoundecapeptide amphisin from Pseudomonas sp. strain DSS73.” Acta Crystallographica Section C57 (2001).

Sorensen, et al. “Cyclic lipoundecapeptide lokisin from Pseudomonas sp. Strain DSS41.” Tetrahedron Letters43 (2002).

Ui, et al. “A novel cyclic lipoundecapeptide, pholipeptin, isolated from Pseudomonas sp.” Tetrahedron36, 41 (1995).

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