Search for transcription factors affecting productivity of the polyketide FR901512 in filamentous fungal sp. No. 14919 and identification of Drf1, a novel negative regulator of the biosynthetic gene cluster

<p>In order to increase secondary metabolite production in filamentous fungi, a transcription factor gene in the biosynthetic gene cluster and global regulator genes such as <i>laeA</i> are considered plausible as targets for overexpression by genetic modification. In this study, we examined these overexpression effect in fungal sp. No. 14919 that produces FR901512, an HMG-CoA reductase inhibitor. Resultantly, the productivity was improved at 1.7–1.8 fold by overexpressing <i>frlE</i>, a transcription factor gene in the biosynthetic gene cluster, whereas productivity did not change by overexpression of <i>laeA</i> and <i>veA</i>. Furthermore, we searched for extra transcription factors affecting the productivity by transcriptome analysis between wild-type strain and highly productive UV mutants. After verifying productivity decrease by overexpression, Drf1, a novel transcription factor encoded by <i>drf1</i> was identified as the negative regulator. Because each <i>frlE</i> product (FrlE) and Drf1 worked on the same cluster in positive and negative regulatory manners, their network was analyzed.</p> <p>By focusing on transcription factors in fungal sp. No. 14919 produces FR901512, we identified Drf1, negative regulation factor of the FR901512 biosynthetic gene cluster.</p>