Novel Aeruginosin‐865 from Nostoc sp. as a Potent Anti‐inflammatory Agent

Abstract

Aeruginosin-865 (Aer-865), isolated from terrestrial cyanobacterium Nostoc sp. Lukešová 30/93, is the first aeruginosin-type peptide containing both a fatty acid and a carbohydrate moiety, and is the first aeruginosin to be found in the genus Nostoc. Mass spectrometry, chemical and spectroscopic analysis as well as one- and two-dimensional NMR and chiral HPLC analysis of Marfey derivatives were applied to determine the peptidic sequence: D-Hpla, D-Leu, 5-OH-Choi, Agma, with hexanoic and mannopyranosyl uronic acid moieties linked to Choi. We used an AlphaLISA assay to measure the levels of proinflammatory mediators IL-8 and ICAM-1 in hTNF-α-stimulated HLMVECs. Aer-865 showed significant reduction of both: with EC50 values of (3.5±1.5) μg mL(-1) ((4.0±1.7) μM) and (50.0±13.4) μg mL(-1) ((57.8±15.5) μM), respectively. Confocal laser scanning microscopy revealed that the anti-inflammatory effect of Aer-865 was directly associated with inhibition of NF-κB translocation to the nucleus. Moreover, Aer-865 did not show any cytotoxic effect.

A Genetic and Chemical Perspective on Symbiotic Recruitment of Cyanobacteria of the Genus Nostoc into the Host Plant Blasia pusilla L.

“…The structure of the compound has been recently characterized as glucuronated aeruginosin 865 (Kapuscik et al, 2013). The fragmentation patterns of m/z 865 detected in this work in genotypes I, II, VI, VIII, and XIV and that of aeruginosin 865 were identical (Supplementary Figure S3B).…”

“…were found in the same mass range as in our samples (Ishida et al, 2009). An antinflammatory peptide with m/z 865 has been previously reported from a number of terrestrial Nostoc strains (Hrouzek et al, 2011; Kapuscik et al, 2013). The structure of the compound was characterized as glucuronated aeruginosin-865 (Kapuscik et al, 2013).…”

“…An antinflammatory peptide with m/z 865 has been previously reported from a number of terrestrial Nostoc strains (Hrouzek et al, 2011; Kapuscik et al, 2013). The structure of the compound was characterized as glucuronated aeruginosin-865 (Kapuscik et al, 2013). Our results show that production of aeruginosins is wide spread through Nostoc lineage.…”

“…Fragmentation patterns of all these molecules share a common feature of a loss of either 176 or 162 Da, which is indicative of the presence of glucuronic acid or a hexose, respectively (Reinhold et al, 1995; Kapuscik et al, 2013). Glycosylation of non-ribosomal peptide and hybrid polyketide-peptide antibiotics in other bacteria is well known and was found to be important for the biological activity of such compounds (Walsh et al, 2001).…”

Separation of Aeruginosin-865 from Cultivated Soil Cyanobacterium (Nostoc sp.) by Centrifugal Partition Chromatography combined with Gel Permeation Chromatography

“…Our group recently reported the isolation of Aeruginosin-865 (Aer-865, Figure 1), a novel aeruginosin-type peptide, from the terrestrial cyanobacterium Nostoc sp. Lukešová 30/93 [2]. In the same investigation, it was shown that Aer-865 exhibits a potent antiinflammatory activity.…”