Biomedicine in the environment: Cyclotides constitute potent natural toxins in plants and soil bacteria

Abstract

Bioactive compounds produced by plants are easily transferred to soil and water and may cause adverse ecosystem effects. Cyclotides are gene-encoded, circular, cystine-rich mini-proteins produced in Violaceae and Rubiaceae in high amounts. Based on their biological activity and stability, cyclotides have promising pharmaceutical and agricultural applications. We report the toxicity of the cyclotides: kalata B1, kalata B2, and cycloviolacin O2 extracted from plants to green algae (Pseudokirchneriella subcapitata), duckweed (Lemna minor L.), lettuce (Lactuca sativa L.), and bacteria extracted from soil measured as [³H]leucine incorporation. Quantification by liquid chromatography-mass spectrometry demonstrated up to 98% loss of cyclotides from aqueous solutions because of sorption to test vials. Sorption was prevented by adding bovine serum albumin (BSA) to the aqueous media. Cyclotides were toxic to all test organisms with EC50 values of 12 through 140 µM (algae), 9 through 40 µM (duckweed), 4 through 54 µM (lettuce), and 7 through 26 µM (bacteria). Cycloviolacin O2 was the most potent cyclotide in all assays examined. This report is the first to document toxic effects of cyclotides in plants and soil bacteria and to demonstrate that cyclotides are as toxic as commonly used herbicides and biocides. Hence, cyclotides may adversely affect soil and aquatic environments, which needs to be taken into account in future risk assessment of cropping systems for production of these highly bioactive compounds.

Circular Proteins from Plants and Fungi

“…In the case of cyclotides, their insecticidal and antimicrobial effects support their role in host defense (28). In addition, phytotoxic activity and activity against soil bacteria have been demonstrated (36). The fact that cyclotides are expressed in a tissuespecific manner may be a reflection of the allelopathic role of cyclotides (37).…”

Cyclotide Structure–Activity Relationships: Qualitative and Quantitative Approaches Linking Cytotoxic and Anthelmintic Activity to the Clustering of Physicochemical Forces

“…Sequence variation is immense: it has been estimated that the number of different cyclotides in Rubiaceae alone exceeds 50,000 [4]. Cyclotides form a combinational peptide library in those plant species that express them, and their function appears to be related to plant defense as reflected in their potent insecticidal [10] and antimicrobial activity [11], [12]. Cyclotides also have pharmaceutically relevant properties including anti-cancer [13] and anti-HIV activity [14], and have proven to be good scaffolds for protein engineering [15].…”

Effect of secochiliolide acid isolated from the Patagonian shrub Nardophyllum bryoides as active component in antifouling paints

“…Based on the previously described problems associated with the sustainability of natural antifoulants of marine origin, the focus of this study was set in the search of a plant extract, or a plant-derived natural product which could be incorporated as active component in an antifouling paint. In this context, recent laboratory experiments employing terrestrial plant extracts detected antimicrobial properties in coconut husk fiber extracts (Viju et al, 2013) and also the production of cyclotides (small proteins) from Rubiaceae and Violaceae with reversible, nontoxic, antisettlement effects on the barnacle Balanus improvisus (Göransson et al, 2004;Ovesen et al, 2011).…”

“…For this reason, an additional effort has to be made in the search of natural antifoulants from more sustainable resources such as abundant and easy collectable terrestrial plants. Comparatively little attention has been given to terrestrial plants in the search for natural products which may act as antifoulants, and only a few antifouling compounds have been reported from these sources (Yamashita et al, 1989;Hyodo et al, 1992;Sawant and Wagh, 1994;Sawant et al, 1995;Göransson et al, 2004;Angarano et al, 2007;Pérez et al, 2007;Chen et al, 2008;Zhou et al, 2009;Ovesen et al, 2011). Plant natural products from abundant and widely distributed species represent an attractive and sustainable source of new bioactive compounds.…”