Structural determination of ananatoside A: An unprecedented 15-membered macrodilactone-containing glycolipid from Pantoea ananatis

Gauthier, Charles; Lavoie, Serge; Piochon, Marianne; Martinez, Sarah; Milot, Sylvain; Déziel, Éric

doi:10.1016/j.carres.2018.10.009

Cited by 13 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reports about rhamnolipid formation by the wild-type strains Enterobacter asburiae (17,18), Enterobacter hormaechei, P. stewartii (17) (Fig. 1), and P. ananatis BRT175, a strain producing a glycolipid with a sugar moiety other than rhamnose (34,41), show similar fatty acid chain lengths to those we detected with pANA and pDAD. Though the HAA spectrum from, e.g., pDAD and pFLU or pHAL and pBUG are similar, the RhlAs are only distantly related and not arranged in the same phylogenetic lineage.…”

Section: Discussionsupporting

confidence: 74%

“…An rhlAB-like operon is found only in Pantoea strains (34) and Lonsdalea britanica, while rhlA homologs are found in Serratia and Dickeya strains but not in synteny with an rhlB homolog. No experimental evidence for HAA or rhamnolipid formation exists for the organisms in this branch, with the exception of Pantoea ananatis BRT175 (P. ananatis) producing the glucolipid ananatoside A, the hydrophobic part of which is an HAA molecule (34,41). In P. ananatis LMG20103, the three genes tcp, ygbK, and kgdT1, which code for a putative methyl-accepting chemotaxis citrate transducer, an effector protein, and a 2-keto-3-deoxygluconate permease, respectively, are encoded in one common operon with the rhlAB homologs.…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

Exploiting the Natural Diversity of RhlA Acyltransferases for the Synthesis of the Rhamnolipid Precursor 3-(3-Hydroxyalkanoyloxy)Alkanoic Acid

Germer

Tiso

Müller

et al. 2020

Appl Environ Microbiol

View full text Add to dashboard Cite

While rhamnolipids of the Pseudomonas aeruginosa type are commercially available, the natural diversity of rhamnolipids and their origin have barely been investigated. Here, we collected known and identified new rhlA genes encoding the acyltransferase responsible for the synthesis of the lipophilic rhamnolipid precursor 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA). Generally, all homologs were found in Betaproteobacteria and Gammaproteobacteria. A likely horizontal gene transfer event into Actinobacteria is the only identified exception. The phylogeny of the RhlA homologs from Pseudomonas and Burkholderia species is consistent with the organism phylogeny, and genes involved in rhamnolipid synthesis are located in operons. In contrast, RhlA homologs from the Enterobacterales do not follow the organisms’ phylogeny but form their own branch. Furthermore, in many Enterobacterales and Halomonas from the Oceanospirillales, an isolated rhlA homolog can be found in the genome. The RhlAs from Pseudomonas aeruginosa PA01, Pseudomonas fluorescens LMG 05825, Pantoea ananatis LMG 20103, Burkholderia plantarii PG1, Burkholderia ambifaria LMG 19182, Halomonas sp. strain R57-5, Dickeya dadantii Ech586, and Serratia plymuthica PRI-2C were expressed in Escherichia coli and tested for HAA production. Indeed, except for the Serratia RhlA, HAAs were produced with the engineered strains. A detailed analysis of the produced HAA congeners by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) highlights the congener specificity of the RhlA proteins. The congener length varies from 4 to 18 carbon atoms, with the main congeners consisting of different combinations of saturated or monounsaturated C10, C12, and C14 fatty acids. The results are discussed in the context of the phylogeny of this unusual enzymatic activity. IMPORTANCE The RhlA specificity explains the observed differences in 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA) congeners. Whole-cell catalysts can now be designed for the synthesis of different congener mixtures of HAAs and rhamnolipids, thereby contributing to the envisaged synthesis of designer HAAs.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Figmentioning

confidence: 99%

Exploiting the Natural Diversity of RhlA Acyltransferases for the Synthesis of the Rhamnolipid Precursor 3-(3-Hydroxyalkanoyloxy)Alkanoic Acid

Germer

Tiso

Müller

et al. 2020

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…Through this optimized procedure, ananatoside A ( 1 ) was isolated as a yellow oil and its physical and analytical data ( R f , specific rotation, HRMS, and 1D and 2D NMR) were in perfect agreement with those we recently published. 26 A more polar and major congener (see Fig. S1 † ), that we have named ananatoside B ( 2 ), was also isolated from the EtOAc extract as a white amorphous powder.…”

Section: Resultsmentioning

confidence: 99%

“…1 ), features an unprecedented 15-membered macrodilactone ring comprising a β- d -glucose residue linked to a C 10 C 10 dilipid chain through both C1 and C6 positions. 26 Biologically active glucolipids containing mono-, di-, and trilactones of different macrocyle sizes have been identified from other microorganisms 29–31 including, to name a few examples, lactonic sophorolipids ( Fig. 1 ), glucolipsins ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Maude Cloutier, 1 Marie-Joëlle Prévost, 1 Serge Lavoie, 2 Thomas Feroldi, 2 Marianne Piochon, 1 Marie-Christine Groleau, 1 Jean Legault, 2 Sandra Villaume, 3 Jérôme Crouzet, 3 Stéphan Dorey, 3 Mayri Alejandra Dìaz De Rienzo, 1,4 (2). Methanol (0.5%) was used as a control.…”

Section: Supplementary Information Total Synthesis Isolation Surfactant Properties and Biological Evaluation Of Ananatosides And Related mentioning

confidence: 99%

Total Synthesis, Isolation, Surfactant Properties, and Biological Evaluation of Ananatosides and Related Macrodilactone-Containing Rhamnolipids

Cloutier¹,

Prévost²,

Lavoie³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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 prove that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity.

show abstract

Structural determination of ananatoside A: An unprecedented 15-membered macrodilactone-containing glycolipid from Pantoea ananatis

Cited by 13 publications

References 24 publications

Exploiting the Natural Diversity of RhlA Acyltransferases for the Synthesis of the Rhamnolipid Precursor 3-(3-Hydroxyalkanoyloxy)Alkanoic Acid

Exploiting the Natural Diversity of RhlA Acyltransferases for the Synthesis of the Rhamnolipid Precursor 3-(3-Hydroxyalkanoyloxy)Alkanoic Acid

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

Total Synthesis, Isolation, Surfactant Properties, and Biological Evaluation of Ananatosides and Related Macrodilactone-Containing Rhamnolipids

Contact Info

Product

Resources

About