P, a Low-pH-Induced Promoter, as a Tool for Dynamic Control of Gene Expression for Metabolic Engineering of Aspergillus niger.

The dynamic control of gene expression is important for adjusting fluxes in order to obtain desired products and achieve appropriate cell growth, particularly when the synthesis of a desired product drains metabolites required for cell growth. For dynamic gene expression, a promoter responsive to a particular environmental stressor is vital. Here, we report a low-pH-inducible promoter, P, which promotes minimal gene expression at pH values above 5.0 but functions efficiently at low pHs, such as pH 2.0. First, we performed a transcriptional analysis of , an excellent platform for the production of organic acids, and we found that the promoter P may act efficiently at low pH. Then, a gene for synthetic green fluorescent protein () was successfully expressed by P at pH 2.0, verifying the results of the transcriptional analysis. Next, P was used to express the -aconitate decarboxylase () gene of in , allowing the production of itaconic acid at a titer of 4.92 g/liter. Finally, we found that P strength was independent of acid type and acid ion concentration, showing dependence on pH only. The promoter P can be used for the dynamic control of gene expression in for metabolic engineering to produce organic acids. This promoter may also be a candidate tool for genetic engineering.