Anikasin

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Anikasin is a non-ribosomal cyclic lipodepsipeptide produced by Pseudomonas bacteria.

Original publication(Klapper, 2016, Götze, 2017)
Original sourcePseudomonas fluorescens HKI0770
Sequence determined byX-ray crystallography
Stereochemistry determined byMarfey’s analysis and X-ray crystallography
Other known sources (non-putative)n.a.

Chemical properties

Molecular formulaC66H111N11O20
Mono-isotopic mass1353.8007 (isobaric to other CLiPs, see text)
Molecular weight1354.6 g mol-1
Solubilityn.a.
CMCn.a.
NMR data availableDMSO-d6 (Götze, 2017)

Structure

Anikasin is a cyclic lipodepsipeptide (CLiP) produced by Pseudomonas fluorescens HKI0770. 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. The primary structure of arthrofactin is 3R-hydroxydecanoyl – D-Leu1- D-Asp2 – D-aThr3 – D-Leu4 – D-Leu5 – D-Ser6 – L-Leu7 – D-Ser8 – L-Leu9 – L-Ile10 – L-Asp11. It cannot be excluded that anikasin is identical to pholipeptin and/or lokisin, as the exact positions of L- and D-amino acids within the latter CLP are unknown.

Figure: Planar structure of anikasin.
Figure: Schematic sequences of anikasin, where shapes indicate amino acid configuration (circles = L-AA, squares = D-AA) and colors indicate amino acid polarity (green = hydrophobic, red = polar)

Anikasin is a member of the amphisin group, a collection of structurally similar lipopeptides including amphisin, tensin, lokisin, arthrofactins, milkisins and stechlisins. The group is also reported to contain two ill-characterized CLiPs: hordersin and pholipeptin. Within the amphisin group, variations mostly occur at position 8 (Gln vs. Ser), position 9 (Leu vs Ile) and position 11 (Asp vs Glu). Anikasin is isobaric to lokisin, arthrofactin and pholipeptin. Consequently, these cannot be discriminated from one another using mass spectrometry alone. More so, since the NMR chemical shifts of anikasin, lokisin and pholipeptin are highly similar to another, it is possible that these three CLiPs are in fact identical.

Bioactivity

Anikasin is essential for the swarming of the producing Pseudomonas strain, as the mutant Δclp lacking CLiP production lost its swarming capabilities. (Klapper, 2016) This has been observed for many other CLiPs. (Raaijmakers, 2010) Moreover, anikasin showed a moderate activity (IC50 = 94 μg mL−1) against Dictyostelium discoideum, a model predator of bacteria. No information is available on its antagonistic activities against other microorganisms.

Three-dimensional structure

Anikasin crystallizes in space group P21 with two molecules and several water molecules in the asymmetric unit. Both molecules are very similar and show the presence of a left-handed helix ranging from D-Leu1 to D-Ser6. From L-Leu7 onwards, the conformation forms 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. The global fold is therefore highly similar to other amphisin group members, such as amphisin and tensin.

Figure: X-ray structure of anikasin.

References

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.

Klapper, et al. “Bacterial alkaloids prevent amoebal predation.” Angewandte Chemie International Edition55, 31 (2016): https://dx.doi.org/10.1002/anie.201603312.

Raaijmakers, et al. “Natural functions of lipopeptides from Bacillus and Pseudomonas.” FEMS Microbiology Reviews34, 6 (2010): https://dx.doi.org/10.1111/j.1574-6976.2010.00221.x.

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