Leucinostatins, Peptide Mycotoxins Produced by Paecilomyces lilacinus and their Possible Roles in Fungal Infection

Peptide mycotoxins “leucinostatins” were obtained from the culture strains of Paecilomyces lilacinus, which were isolated both from soil and a case of human oculomycosis. Comparative studies of the symptoms of experimental keratomycosis caused both by the inoculation of P. lilacinus and by direct administration of leucinostatins into the infection model in rabbit suggested the possible role of leucinostatins in the inflammatory response of invaded tissues. Leucinostatin was formerly reported as a single entity. However, in the course of the structural studies, leucinostatin was found to be a complex of two closely related components, and the structures of the both mycotoxins were determined. Both of the mycotoxins possessed high toxicity to experimental animals. The intraperitoneal and oral LD₅₀ values in mice were 1.8 and 5.4 to 6.3 mg/kg by a single administration. Toxicological studies showed that leucinostatins have some potent effects on liver cells after oral administration. It was also found that leucinostatins exhibit strong uncoupling activity on rat liver mitochondrial system.