Characterization, Diversity, and Structure-Activity Relationship Study of Lipoamino Acids from Pantoea sp. and Synthetic Analogues

Abstract

A biological evaluation of a library of extracts from entomopathogen strains showed that Pantoea sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS spectroscopic data. The antimicrobial and insecticidal potencies of these compounds were evaluated, and compound 3 showed 67% mortality against Aedes aegypti larvae at a concentration of 100 ppm, and a minimum inhibitory concentration (MIC) of 16 µg/mL against methicillin-resistant Staphylococcus aureus. Subsequently, hydroxyacyl-phenylalanine analogues were synthesized to better understand the structure-activity relationships within this class of compounds. Bioassays highlighted the antimicrobial potential of analogues containing saturated medium-chain fatty acids (12 or 14 carbons), whereas an unsaturated long-chain fatty acid (16 carbons) imparted larvicidal activity. Finally, using a molecular networking-based approach, several close analogues of the isolated and newly synthesized lipoamino acids were discovered in the Pantoea sp. extract.

Molecular Network and Culture Media Variation Reveal a Complex Metabolic Profile in Pantoea cf. eucrina D2 Associated with an Acidified Marine Sponge

“…Our results parallel those reported by Tourè et al [ 8 ] in what concerns the qualitative composition of the mixture except for some congeners. Although our Pantoea cf.…”

“…The results reported in Table 2 show that this class of molecules is ineffective against the Gram-negative strains ( Acinetobacter baumannii 13 and Stenotrophomonas maltophilia ATCC 13637). In addition, the amino acid moiety seems to play an important role in the exertion of antimicrobial properties, in fact, in accordance with a recent report on phenylalanine lipoamino acids [ 8 ], Compounds 6 – 8 are totally ineffective or slightly active towards Staphylococcus aureus and also against Staphylococcus epidermidis , independently from fatty acid chain length. On the other hand, leucine- containing congeners were very active towards Staphylococcus spp., with the best MIC values given by Compounds 1 , 3 and 4 with 10 (μg/mL) towards S. aureus and by Compounds 3 and 4 with 10 (μg/mL) towards S. epidermidis .…”

“…Through NMR and MS analysis and by comparison with literature data [ 8 ] Compounds 6 , 7 and 8 were identified as N -palmitoyl- l -phenylalanine, N -palmitenoyl- l -phenylalanine and N -oleyl- l -phenylalanine, respectively. N -palmitenoyl- l -phenylalanine ( 7 ) was already isolated from Pantoea sp., whereas Compounds 6 and 8 were obtained in the same study by synthesis [ 8 ].…”

“…Through NMR and MS analysis and by comparison with literature data [ 8 ] Compounds 6 , 7 and 8 were identified as N -palmitoyl- l -phenylalanine, N -palmitenoyl- l -phenylalanine and N -oleyl- l -phenylalanine, respectively. N -palmitenoyl- l -phenylalanine ( 7 ) was already isolated from Pantoea sp., whereas Compounds 6 and 8 were obtained in the same study by synthesis [ 8 ]. The configuration of the double bond in the acyl chain of 7 and 8 was assigned as Z on the basis of the 13 C NMR chemical shifts of allylic methylenes, whereas the L-configuration of the phenylalanine residue was assigned by comparison of the experimental positive optical rotation data with those reported in the literature [ 8 ].…”

“…The study of the phenotypic features of members of this species has been so far mainly focused on the comparative genomic analysis in the search for the genetic and genomic determinants able to drive specific diversity and adaptability [ 6 , 7 , 8 ], whereas there are only sporadic papers dealing with the chemical profiling of members of this genus.…”