Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in F913.

Nigericin is a polyether antibiotic with potent antibacterial, antifungal, antimalarial and anticancer activity. NigR, the only regulator in the nigericin biosynthetic gene cluster in F913, was identified as a SARP family regulator. Disruption of abolished nigericin biosynthesis, while complementation of restored nigericin production, suggesting that NigR is an essential positive regulator for nigericin biosynthesis. Overexpression of in led to significant increase in nigericin production compared to the wild-type strain. Nigericin production in the overexpression strain was found to reach 0.56 g/L, which may be the highest nigericin titer reported to date. Transcriptional analysis suggested that is required for the transcription of structural genes in the gene cluster; quantitative RT-PCR analysis revealed that the expression of structural genes was upregulated in the overexpression strain. Our study suggested that NigR acts in a positive manner to modulate nigericin production by activating transcription of structural genes and provides an effective strategy for scaling up nigericin production.