Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions

Abstract

We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation.

Fungi and their secondary metabolites in water‐damaged indoors after a major flood event in eastern Croatia

“…The acute oral toxicity of STC is relatively low and related to liver and kidney damage; chronic respiratory exposure of Wistar rats to STC‐producing Aspergilli provoked lesions in the lung and pleura and lung and endocrine organs tumor development 45 . Additionally, a recent study revealed that STC possesses unique aggregation properties in water, yielding a strong and specific circular dichroism spectrum which showed that STC interacts with DNA strongly and non‐covalently, with likely toxic effects which is contrary to requiring prior enzymatic epoxidation 46 . A few studies on human lung cell cultures revealed the cytotoxic and genotoxic potential of both STC and 5‐MET‐STC as well as the cytotoxicity of STC‐producing Aspergilli ( Versicolores ) 4,34,43,47,48 .…”

“…45 Additionally, a recent study revealed that STC possesses unique aggregation properties in water, yielding a strong and specific circular dichroism spectrum which showed that STC interacts with DNA strongly and non-covalently, with likely toxic effects which is contrary to requiring prior enzymatic epoxidation. 46 A few studies on human lung cell cultures revealed the cytotoxic and genotoxic potential of both STC and 5-MET-STC as well as the cytotoxicity of STC-producing Aspergilli (Versicolores). 4,34,43,47,48 Altogether, we emphasize the health threats to inhabitants of post-flooded dwellings posed by indoor mold contamination and inhalation of STC and 5-MET-STC.…”

Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins

“…This may be explained by the additional methoxy group, an electron-donating group that activates the electrophilic hydroxyl group of 5-M-STC and thus may improve the bioavailability of 5-M-STC. Additionally, the lower cytotoxic potential of STC in comparison to 5-M-STC could be attributed to STC’s unique aggregation properties in water at concentrations between 5 and 10 μM, yielding a strong and specific circular dichroism spectrum [ 30 ]. Increasing the concentration of STC also increases the aggregation process, which in turn could decrease cell bioavailability.…”

Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs

“…In porcine primary tracheal epithelial cells treated with STC (50 μM), CYP enzymes produced a reactive STC metabolite [ 18 ], which may interact with DNA, leading to DNA single-strand breaks. On the other hand, a recent study revealed that STC at concentrations between 5 and 10 μM possesses unique aggregation properties in water, yielding a strong and specific circular dichroism spectrum [ 34 ]. Data showed that STC non-covalently interacts with DNA, most probably by intercalation between base pairs, which may result in DNA double-strand breaks [ 34 ].…”

“…On the other hand, a recent study revealed that STC at concentrations between 5 and 10 μM possesses unique aggregation properties in water, yielding a strong and specific circular dichroism spectrum [ 34 ]. Data showed that STC non-covalently interacts with DNA, most probably by intercalation between base pairs, which may result in DNA double-strand breaks [ 34 ]. We can only speculate whether both mechanisms may be in action, depending on the bioavailable concentration of STC and CYP activity.…”