Complexation of the mycotoxin cyclopiazonic acid with lanthanides yields luminescent products

Authors: Maragos, Chris

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/2/2018
Publication Date: 7/10/2018
Citation: Maragos, C.M. 2018. Complexation of the mycotoxin cyclopiazonic acid with lanthanides yields luminescent products. Toxins. 10(7):285. https://doi.org/10.3390/toxins10070285.
DOI: https://doi.org/10.3390/toxins10070285

Interpretive Summary: Cyclopiazonic acid (CPA) is a neurotoxin that is made by some of the same fungi that make the more widely known aflatoxins. The toxin acts by altering calcium levels within cells. CPA has been found as a natural contaminant in cheeses, figs, maize, rice, peanuts, millet, feeds, and meat. Data on exposure of people to CPA is limited, in part because the tools for its measurement are also limited. An ARS scientist in Peoria, IL, has developed a method that can render CPA fluorescent, which greatly facilitates its detection. The method, which is based upon the metal Terbium, was used to determine the relative binding of 10 metals to CPA. Determining how CPA binds with metals is important to revealing how this toxin interacts with its target enzyme, and therefore the mechanism wherein it exerts its toxic effects. Knowing the mechanism of action will help efforts to mitigate the potential effects of exposure.

Technical Abstract: Cycopiazonic acid (CPA) is a neurotoxin that acts through inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). CPA blocks the calcium access channel of the enzyme. The inhibition may involve the binding of CPA with a divalent cation such as Mg2+. The potential for CPA to act as a chelator also has implications for methods to detect this toxin. Certain of the lanthanide metals undergo a dramatic increase in luminescence upon coordination with small molecules that can transfer excitation energy to the metal. This report is the first to describe the coordination of CPA with lanthanide metals, resulting in a substantial enhancement of their luminescence. The luminescence expressed was dependent upon the type of lanthanide, its concentration, and the environment (solvent, water content, pH). Based upon the phenomenon, a competitive assay was also developed wherein terbium (Tb3+) and a series of metal cations competed for binding with CPA. With increasing cation concentration, the luminescence of the CPA/Tb3+ complex was inhibited. The chlorides of ten metals were tested. Inhibition was best with Cu2+, followed by Co2+, Al3+, Fe3+, Mn2+, Au3+, Mg2+, and Ca2+. Two cations in oxidation state one (Na+, K+) did not inhibit the interaction significantly. The interaction of CPA with lanthanides provides a novel recognition assay for this toxin. It also provides a novel way to probe the binding of CPA to metals, giving insights into CPA’s mechanism of action.