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) and sclerotiotide C (3), and kojic acid (4) and penicillic acid (5). Bioassays revealed that compound 2 displayed promising antimicrobial effects on Candida albicans with a MIC value of 32 µg/mL and 4 exhibited significant antioxidant activity with the similar IC50 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–nonribosomal peptide synthetase (PKS/NRPS) hybrids and amino acid metabolism, demonstrating an effective approach for a production of cyclic lipopeptides.