Sporogen-AO1 inhibits eukaryotic translation elongation.

Sporogen-AO1, a sporulation-promoting substance of Aspergillus oryzae was found to be a nonspecific translation inhibitor during screening of 22400 compounds. Sporogen-AO1 inhibited protein synthesis in cell-free protein synthesis (CFPS) systems derived from HeLa cell, wheat germ and yeast extracts, but not from E. coli S30 extracts. Sporogen-AO1 inhibited translation initiated from the cricket paralysis virus internal ribosome entry site, which does not require any translation initiation factor. Inhibition of translation due to sporogen-AO1was also observed in a CFPS system reconstituted with human translation factors and ribosomes; sporogen-AO1 decreased translation in the reconstituted CFPS system lacking aminoacyl-tRNA synthetases or translation termination factors. Thus, sporogen-AO1 targets the translation elongation phase comprising the ribosome and translation elongation factors. The IC values of sporogen-AO1 and cycloheximide were 7.44 ± 1.63 μM and 0.17 ± 0.05 μM, respectively, meaning that sporogen-AO1 can act as a relatively mild inhibitor against eukaryotic translation elongation.