Xantholysin B-C

General info

Original publication	Li, 2013
Original source	Pseudomonas mosselii BW11M1
Other known sources (non-putative)	Pseudomonas sp. 250J (Molina-Santiago, 2015) Pseudomonas sp. DJ15 (Lim, 2017)
Stereochemistry determined by	Minor compounds of xantholysin A, produced by Pseudomonas mosselii BW11M1

Chemical properties

CAS	n.a.
Molecular formula	C83H144N18O23 (xantholysin B) C86H148N18O23 (xantholysin C)
Molecular weight	1762.2 Da (xantholysin B) 1802.1 Da (xantholysin C)
Mono-isotopic mass	1761.0652 (xantholysin B) 1801.0965 (xantholysin C)
Solubility	Methanol, chloroform, acetone, buffer, DMF Not soluble (or very limited) in milliQwater
CMC	n.a.
Minimal surface tension	n.a.
3D conformation	n.a.
NMR data available in literature	n.a.

Introduction

The original xantholysin-producer, Pseudomonas mosselii BW11M1 (originally Pseudomonas putida BW11M1), was isolated from the banana rhizosphere in Sri Lanka in the context of a study aimed at screening for natural compounds that display inhibitory activity against Xanthomonas bacteria. (Vlassak, 1992). By using several knock-out mutants, it was observed that the antimicrobial activity of P. mosselii BW11M1 was exerted by the cyclic lipodepsipeptide (CLiP) xantholysin. (Li, 2013) This CLiP consists of a partially cyclized 14-amino acid peptide sequence. The N-terminus of the peptide is capped by a fatty acid moiety. Together with the main lipopeptide, xantholysin A, multiple structural homologues were extracted from the bacterium in minor quantities. These minors are named xantholysin B and C.

Chemical structure

The structure of xantholysin B and C was first elucidated in 2013 by means of liquid state NMR spectroscopy and mass spectrometry. (Li, 2013) They consists of a cyclic peptide consisting of 14 amino acids, of which 8 are contained in the macrocycle. The N-terminal of the peptide is capped by a fatty acid tail. Xantholysin B differs from xantholysin A only at the C-terminal position 14, where is possesses a valine instead of isoleucine. Xantholysin C only differs from the A homologue in its fatty acid, where it features a 3-hydroxy dodecenoic acid (3-OH C12:1) instead of a 3-hydroxy decanoic acid (3-OH C10:0).

The stereochemistry of the main lipopeptide of P. mosselii BW11M1, xantholysin A, was elucidated very recently by means of total synthesis and NMR fingerprint matching. (De Roo, 2022) Given the fact that xantholysins B and C are minor homologues of xantholysin A and these compounds are produced by the same NRPS system, it stands to reason that they feature the same stereochemical make-up.

Taken together, the structure of xantholysin B is 3R-OH C10:0 – L-Leu1 – D-Glu2 – D-Gln3 – D-Val4 – D-Leu5 – L-Gln6 – D-Ser7 – D-Val8 – D-Leu9 – D-Gln10 – L-Leu11 – L-Leu12 – D-Gln13 – L-Val14 while that of xantholysin C is 3R-OH C12:1 – L-Leu1 – D-Glu2 – D-Gln3 – D-Val4 – D-Leu5 – L-Gln6 – D-Ser7 – D-Val8 – D-Leu9 – D-Gln10 – L-Leu11 – L-Leu12 – D-Gln13 – L-Ile14. In both cases, the molecules are cyclized by means of an ester bond between the C-terminus and the side chain hydroxyl moiety of serine at position 7. The structures of xantholysins bear a single negative charge at physiological pH due to the presence of a glutamic acid at position 2.

References

De Roo, et al. “An Nuclear Magnetic Resonance Fingerprint Matching Approach for the Identification and Structural Re-Evaluation of Pseudomonas Lipopeptides.” Microbiology Spectrum10, 4 (2022): https://dx.doi.org/doi:10.1128/spectrum.01261-22.

Li, et al. “The antimicrobial compound xantholysin defines a new group of Pseudomonas cyclic lipopeptides.” PLoS One8, 5 (2013): https://dx.doi.org/10.1371/journal.pone.0062946.

Lim, et al. “Identification of lipopeptide xantholysins from Pseudomonas sp. DJ15 and their insecticidal activity against Myzus persicae.” Entomological Research47, 6 (2017): https://dx.doi.org/10.1111/1748-5967.12241.

Molina-Santiago, et al. “Efflux pump-deficient mutants as a platform to search for microbes that produce antibiotics.” Microbial Biotechnology8, 4 (2015): https://dx.doi.org/10.1111/1751-7915.12295.

Vlassak, et al. “Isolation and characterization of fluorescent Pseudomonas associated with the roots of rice and banana grown in Sri Lanka.” Plant and Soil145, 1 (1992): https://dx.doi.org/10.1007/BF00009541.