Discovery of the 2,4′-Dihydroxy-3′-methoxypropiophenone Biosynthesis Genes inAspergillus oryzae

The filamentous fungusAspergillus oryzaehas 27 putative iterative type I polyketide synthase (PKS) gene clusters, but the secondary metabolites produced by them are mostly unknown. Here, we focused on eight clusters that were reported to be expressed at relatively high levels in a transcriptome analysis. By comparing metabolites between an octuple-deletion mutant of these eight PKS gene clusters and its parent strain, we found thatA. oryzaeproduced 2,4 '-dihydroxy-3 '-methoxypropiophenone (1) and its precursor, 4 '-hydroxy-3 '-methoxypropiophenone (3) in a specific liquid medium. Furthermore, an iterative type I PKS (PpsB) encoded by AO090102000166 and an acetyl-CoA ligase (PpsA) encoded downstream fromppsBwere shown to be essential for their biosynthesis. PpsC, encoded upstream fromppsB, was shown to have3-binding activity (K-d=26.0 +/- 6.2 mu M) and is suggested to be involved in the conversion of3to1. This study deepens our understanding of cryptic secondary metabolism inA. oryzae.

Automated summary

The filamentous fungus Aspergillus oryzae has 27 putative iterative type I polyketide synthase (PKS) gene clusters, with unknown secondary metabolites. This study focused on eight clusters expressed at high levels, revealing the biosynthesis of 2,4'-dihydroxy-3'-methoxypropiophenone and its precursor, and the essential roles of PpsB and PpsA in their production. PpsC was also implicated in the conversion process from 3 to 1.