Overexpression of a pathway-specific transcriptional factor CicD leads to the discovery of new phytotoxins in Aspergillus nidulans

Abstract

A NRPKS gene cluster cic in Aspergillus nidulans was activated by overexpression of the pathway-specific transcriptional factor CicD. Large-scale fermentation and chemical investigation of the engineered strain A. nidulans A1145/cicD led to the discovery of two new isoindolone-amino acid adducts, isoleucylcichorine (1) and leucylcichorine (2), along with three known derivatives. The structures of the new compounds were clearly determined by nuclear magnetic resonance (NMR) analysis, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. This study revealed that the overexpression of the pathway-specific transcriptional factor represents a promising approach for the discovery of new natural products in fungi.