FKI-6682A and FKI-6324A, new mitochondrial respiration inhibitors discovered by pesticide screening using recombinant Saccharomyces cerevisiae

It is important to develop new pesticides to overcome the drug-resistant mechanisms in agricultural pest. It is also conceivable that a novel pesticide might lead to the discovery of new mode of action. In this regard, we have commenced a screening program to find new pesticides from microbial metabolites using screening system of recombinant Saccharomyces cerevisiae. Recently, we discovered that the fungi Aspergillus sp. and Tricoderma sp. isolated from soil samples produced two new pesticide candidates designated as FKI-6682A (1) and FKI-6324A (2), respectively. The structure of 1 was elucidated by detailed NMR experiments to have a lanostane skeleton and a sugar moiety. Interestingly, this structural frame is similar to that of ascosteroside (3). Compounds 1 and 3have unique characteristics such as the presence of an exomethylene group and a carboxylic acid in lanostane skeleton. On the other hand, the planar structure of 2 with aminoisobutyric acids was established by detailed product ion mass spectra and ¹H-NMR, gCOSY and HSQC to have containing methyldecanoic acid, 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid and trichodiaminol moiety. The core structure of 2 was similar to that of trichopolyn analogues isolated from fungal metabolites. The structure of 2 is different from the structure of trichopolyn ² as regards the H-6 and H-7 positions. We report the isolation, structural elucidation, and biological activity of 1 and 2 in this meeting.

The study was supported by Programme for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry.