Overexpression of the Global Transcriptional Regulator LaeA Leads to Production of Cyclic Lipopeptides in Marine-Derived Aspergillus niger L14.

Overexpression of a global transcriptional regulator LaeA was performed to awaken cryptic biosynthetic gene clusters (BGCs) in a marine sponge-derived fungus, Aspergillus niger L14, to obtain secondary metabolites (SMs), and resulted in the production of five previously undiscovered SMs in the wild-type strain, including three cyclic lipopeptides aspochracin (1), JBIR-15 (2) sclerotiotide C (3), kojic acid (4) and penicillic acid (5). Bioassays revealed that compound 2 displayed promising antimicrobial effects on Candida albicans with a minimum inhibitory concentration value of 32 µg/mL and 4 exhibited significant antioxidant activity with a similar half-maximal inhibitory concentration value (5 µg/mL) to that of ascorbic acid. Transcriptome analysis results indicated that the overexpression of LaeA in strain L14 remarkably enhanced the expression of genes involved in polyketide synthase-non-ribosomal peptide synthetase hybrids and amino acid metabolism, demonstrating an effective approach for the production of cyclic lipopeptides.