MoLAEA Regulates Secondary Metabolism in Magnaporthe oryzae

Fungi are rich sources of secondary metabolites of pharmaceutical im-portance, such as antibiotics, antitumor agents, and immunosuppressants, as well as of harmful toxins. Secondary metabolites play important roles in the development and pathogenesis of fungi. LaeA is a global regulator of secondary metabolism and was originally reported in Aspergillus nidulans; however, its role in secondary metab-olism in Magnaporthe oryzae has not yet been reported. Here, we investigated the role of a gene homologous to LAEA (loss of AflR expression) of Aspergillus spp. in Magnaporthe oryzae , named M. oryzae LAEA (MoLAEA ). Studies on MoLAEA overex-pression and knockdown strains have suggested that this gene acts as a negative regulator of sporulation and melanin synthesis. However, it is not involved in the growth and pathogenesis of M. oryzae . Transcriptomic data indicated that MoLAEA regulated genes involved in secondary metabolism. Interestingly, we observed (for the first time, to our knowledge) that this gene is involved in benzylpenicillin (peni-cillin G) synthesis in M. oryzae . Overexpression of MoLAEA increased penicillin G pro-duction, whereas the silenced strain showed a complete absence of penicillin G compared to its presence in the wild type. We also observed that Mo LaeA interacted with Mo VeA, a velvet family protein involved in fungal development and secondary metabolism, in the nucleus. This study showed that though MoLAEA may not make any contribution in rice blast fungal pathogenesis, it regulates secondary metabo-lism in M. oryzae and thus can be further studied for identifying other new unchar-acterized metabolites in this fungus. IMPORTANCE M. oryzae causes blast disease, the most serious disease of cultivated rice affecting global rice production. The genome of M. oryzae has been shown to have a number of genes involved in secondary metabolism, but most of them are uncharacterized. In fact, compared to studies of other filamentous fungi, hardly any work has been done on secondary metabolism in M. oryzae . It is shown here (for the first time, to our knowledge) that penicillin G is being synthesized in M. oryzae and that MoLAEA is involved in this process. This is the first step in understanding the penicillin G biosynthesis pathway in M. oryzae . This study also unraveled the details of how Mo LaeA works by forming a nuclear complex with Mo VeA in M. oryzae , thus indicating functional conservation of such a gene across filamentous fungi. All these findings open up avenues for more relevant investigations on the genetic regulation of secondary metabolism in M. oryzae.