# A Toxic Sterolysin From a 1950s Culture of Gymnodinium Veneficum Ballantine

## TL;DR

This paper identifies and characterizes two toxic molecules from a 1950s dinoflagellate culture, showing how they form pores in cell membranes and cause toxicity in fish.

## Contribution

The first functional characterization of karlotoxin-induced membrane pores and their sterol-specific mechanism.

## Key findings

- Two toxins, Abbotoxin and 59-E-Chloro-Abbotoxin, were isolated and identified as karlotoxin congeners.
- Karlotoxins form large-conductance, non-selective channels in lipid membranes with complex voltage-dependent gating.
- Sterol-specific binding is essential for karlotoxin pore formation, particularly involving desmethyl sterols.

## Abstract

In 1957 Abbott and Ballentine described a highly toxic activity from a dinoflagellate isolated from the English Channel. in 1949 by Mary Park. From a culture maintained at Plymouth Laboratory since 1950, we have been able to isolate two toxic molecules (Abbotoxin and 59-E-Chloro-Abbotoxin), determine the planar structures by analysis of HRMS and 1D and 2D NMR spectra and found them to be karlotoxin (KmTx) congeners. Both toxins kill larval zebrafish with symptoms identical to that described by Abbot and Ballantine for gobies (Gobius virescens). Using surface plasma resonance the sterol binding specificity of karlotoxins is shown to require desmethyl sterols. Our results with black lipid membranes indicate that karlotoxin forms large-conductance channels in the lipid membrane, which are characterized by large ionic conductance, poor ionic selectivity, and a complex gating behavior that exhibits strong voltage dependence and multiple gating patterns. In addition, we show that KmTx 2 pore formation is a highly targeted mechanism involving sterol-specificity. This is the first report of the functional properties of the membrane pores formed by karlotoxins and are consistent with the intial observations of Abbott and Ballentine from 1957.