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Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids

Cloutier, M, Prévost, MJ, Lavoie, S, Feroldi, T, Piochon, M, Groleau, MC, Legault, J, Villaume, S, Crouzet, J, Dorey, S, Diaz De Rienzo, MA, Déziel, E and Gauthier, C (2021) Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids. Chemical Science, 12. ISSN 2041-6520

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Abstract

Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogenPseudomonas aeruginosa. The non-human pathogenic bacteriumPantoea ananatisis an alternative producer of rhamnolipid-like metabolites containing glucose instead of rhamnose residues. Herein, we present the isolation, structural characterization, and total synthesis of ananatoside A, a 15-membered macrodilactone-containing glucolipid, and ananatoside B, its open-chain congener, from organic extracts ofP. ananatis. Ananatoside A was synthesized through three alternative pathways involving either an intramolecular glycosylation, a chemical macrolactonization or a direct enzymatic transformation from ananatoside B. A series of diasteroisomerically pure (1→2), (1→3), and (1→4)-macrolactonized rhamnolipids were also synthesized through intramolecular glycosylation and their anomeric configurations as well as ring conformations were solved using molecular modeling in tandem with NMR studies. We show that ananatoside B is a more potent surfactant than its macrolide counterpart. We present evidence that macrolactonization of rhamnolipids enhances their cytotoxic and hemolytic potential, pointing towards a mechanism involving the formation of pores into the lipidic cell membrane. Lastly, we demonstrate that ananatoside A and ananatoside B as well as synthetic macrolactonized rhamnolipids can be perceived by the plant immune system, and that this sensing is more pronounced for a macrolide featuring a rhamnose moiety in its native1C4conformation. Altogether our results suggest that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity.

Item Type: Article
Uncontrolled Keywords: 03 Chemical Sciences
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Royal Society of Chemistry
Date Deposited: 21 Jun 2021 11:08
Last Modified: 21 Jun 2021 11:15
DOI or Identification number: 10.1039/d1sc01146d
URI: https://researchonline.ljmu.ac.uk/id/eprint/15159

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