Abstract
Cyclic lipodepsipeptides produced by Pseudomonas spp. (Ps-CLPs) are biosurfactants that constitute a diverse class of versatile bioactive natural compounds with promising application potential. While chemically diverse, they obey a common structural blue-print, allowing the definition of 14 distinct groups with multiple structurally homologous members. In addition to antibacterial and antifungal properties the reported activity profile of Ps-CLPs includes their effect on bacterial motility, biofilm formation, induced defense responses in plants, their insecticidal activity and anti-proliferation effects on human cancer cell-lines. To further validate their status of potential bioactive substances, we assessed the results of 775 biological tests on 51 Ps-CLPs available from literature. From this, a fragmented view emerges. Taken as a group, Ps-CLPs present a broad activity profile. However, reports on individual Ps-CLPs are often much more limited in the scope of organisms that are challenged or activities that are explored. As a result, our analysis shows that the available data is currently too sparse to allow biological function to be correlated to a particular group of Ps-CLPs. Consequently, certain generalizations that appear in literature with respect to the biological activities of Ps-CLPs should be nuanced. This notwithstanding, the data for the two most extensively studied Ps-CLPs does indicate they can display activities against various biological targets. As the discovery of novel Ps-CLPs accelerates, current challenges to complete and maintain a useful overview of biological activity are discussed.
Highlights
Cyclic lipodepsipeptides (CLPs) are secondary metabolites with a broad array of biological functions
The second one is exemplified by the fact that several CLP-producing bacteria, including Pseudomonas spp., are registered with the United States Environmental Protection Agency (EPA) for biocontrol of plant diseases linked to CLP metabolite production (Olorunleke et al, 2015b) illustrating their potential in agriculture
We focus on the biological activity of CLPs originating from Pseudomonas spp. (Ps-CLPs) as other reviews are available that cover those of other organisms in considerable detail (Perez-Garcia et al, 2011; Cochrane and Vederas, 2016; Kleijn and Martin, 2017)
Summary
Cyclic lipodepsipeptides (CLPs) are secondary metabolites with a broad array of biological functions. Total synthesis of the enantiomer of pseudodesmin A, a member of the viscosin group, was used to exclude chiral, receptor-based interactions as the main determinant of the biological activity since the enantiomer proved as active as the natural compound (De Vleeschouwer et al, 2014) Despite these reports, the detailed molecular events leading to pore-formation, once individual molecules have been incorporated, and the exact relation to Ps-CLP sequence and structure remains to be established. The detailed molecular events leading to pore-formation, once individual molecules have been incorporated, and the exact relation to Ps-CLP sequence and structure remains to be established In this respect it was proposed that the self-assembly of viscosin group Ps-CLPs potentially plays an (indirect) role in the biological activity of these CLPs, as it could be an import factor in the creation of pore-like structures through the cellular membrane (Sinnaeve et al, 2009a; Geudens et al, 2014). It is hoped that the growing interest in Ps-CLPs, combined with the biological data reviewed here and the further development of efficient synthesis route to Ps-CLP will stimulate detailed biophysical studies into their mechanism of action
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