Issue 21, 2021

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

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 pathogen Pseudomonas aeruginosa. The non-human pathogenic bacterium Pantoea ananatis is 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 of P. 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 native 1C4 conformation. Altogether our results suggest that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
25 Febr. 2021
Accepted
22 Apr. 2021
First published
04 Maijs 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 7533-7546

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

M. Cloutier, M. Prévost, S. Lavoie, T. Feroldi, M. Piochon, M. Groleau, J. Legault, S. Villaume, J. Crouzet, S. Dorey, M. A. Dìaz De Rienzo, E. Déziel and C. Gauthier, Chem. Sci., 2021, 12, 7533 DOI: 10.1039/D1SC01146D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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