Collaborative Type I and Type III Polyketide Synthases Produce Unique Benzoquinones Affecting the Growth of Rice Roots

Fungal quinones are widely distributed in nature, display various bioactivities, and are exploited for biotechnological and pharmaceutical applications. Here, we used genome mining in Sarocladium oryzae to identify a gene cluster harboring both type I and III polyketide synthases (PKSs). We reconstructed the biosynthetic pathway via in vitro reactions with purified recombinant enzymes and in vivo total biosynthesis in Aspergillus nidulans and Saccharomyces cerevisiae. The resulting new benzoquinones, saroetins A and B, feature a rare gem-dimethyl moiety installed by the C-methyltransferase domain of the type I PKS. Saroetins are redox-active, and their hydroquinone state can reduce Fe(III) to Fe(II). Saroetin B impedes rice seedlings root growth, induces the accumulation of hydrogen peroxide, and modulates antioxidant enzyme activities. This study broadens our understanding of the catalytic repertoire of fungal collaborative type I and type III PKSs and provides enzymatic tools for expanding the chemical diversity of aromatic polyketides.