Bidirectional Regulation of AdpA in Controlling the Expression of and in the Natamycin Biosynthesis of L10.

AdpA, an AraC/XylS family protein, had been proved as a key regulator for secondary metabolism and morphological differentiation in . Here, we identify AdpA, an ortholog of AdpA, as a "higher level" pleiotropic regulator of natamycin biosynthesis with bidirectional regulatory ability in L10. DNase I footprinting revealed six AdpA-binding sites in the - intergenic region. Further analysis using the reporter gene fused to the - intergenic region of mutated binding sites demonstrated that the expression of and was under the control of AdpA. AdpA showed a bi-stable regulatory ability where it firstly binds to the Site C and Site D to activate the transcription of the two pathway-specific genes, and , and then binds to other sites where it acts as an inhibitor. When Site A and Site F were mutated , the production of natamycin was increased by 21% and 25%, respectively. These findings indicated an autoregulatory mechanism where AdpA serves as a master switch with bidirectional regulation for natamycin biosynthesis.