September 26, 2016
Understanding astellolide biosynthesis (a secondary metabolite) in koji mold
RIKEN CSRS and the Noda Institute for Scientific Research have discovered a novel sesquiterpene cyclase, AstC, from their joint analysis of astellolides in the filamentous fungi Aspergillus oryzae, commonly known as koji mold.
The researchers successfully enhanced production of astellolides in A. oryzae by disrupting its chromatin-remodeling factors. They also succeeded in isolating the gene cluster responsible for astellolide biosynthesis, successfully predicting that the astC gene would be responsible for the novel sesquiterpene cyclase. Analyses of recombinant enzyme reactions revealed that AstC uses a different mechanism than other sesquiterpenes to catalyze cyclization reactions. Researchers also determined that two other enzymes from the isolated gene cluster, AstI and AstK, catalyze dephosphorylation reactions in cyclized sesquiterpenes. Moreover, they found that the esterification of aryl acid to sesquiterpene cyclization products was driven by non-ribosomal peptide synthetase, which is known to catalyze amide bonding reactions.These finding uncover the previously unknown function of AstC, identifying it from the astellolide biosynthesis gene cluster as a novel sesquiterpene cyclase. Given that genes homologous to AstC are widely present in filamentous fungi, these findings should lead to the discovery of new bioactive terpene compounds.
Scientific reports doi:10.1038/srep32865
Y. Shinohara, S. Takahashi, H. Osada, Y. Koyama,
"Identification of a novel sesquiterpene biosynthetic machinery involved in astellolide biosynthesis".
Chemical Biology Research Group