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Updated: Sep 5, 2026
Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
Published on: March 12, 2020
Integration of genome mining and HiTES reveals secondary metabolic potential in marine-derived Aspergillus sp.
Hua-Wei Lv1, Xiao-Ting Liu1, Yi-Jiang Zhou1
1College of Pharmaceutical Science and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang Key Laboratory of Green, Low-Carbon, and Efficient Development of Marine Fishery Resources, Zhejiang University of Technology, Hangzhou 310014, China.
Aims:
Marine-derived Aspergillus species are prolific producers of bioactive secondary metabolites, yet the majority of their biosynthetic gene clusters (BGCs) remain silent. This study aimed to integrate genome mining with high-throughput elicitor screening (HiTES) to unlock the metabolic potential of Aspergillus sp. WHUF0304 and identify elicitors that promote the accumulation of previously undetected metabolites.
Methods And Results:
A high-quality genome of Aspergillus sp. WHUF0304 was assembled and annotated using multiple functional databases, revealing substantial secondary metabolic potential. antiSMASH analysis identified diverse BGCs, including NRPS/indole-related clusters potentially associated with indole diketopiperazine biosynthesis. A HiTES-inspired elicitor screening strategy was then applied to evaluate 42 small molecules for their ability to alter the metabolite profile of this strain. Among the tested elicitors, fluconazole was identified as the optimal inducer, triggering the production of several indole diketopiperazine-related differential metabolites. Subsequent activity-guided isolation led to the identification of a bioactive indole diketopiperazine dimer, cristatumin E, which exhibited antibacterial activity against Escherichia coli and Bacillus subtilis with minimum inhibitory concentrations (MICs) of 32 µg mL-1 and 256 µg mL-1, respectively.
Conclusions:
These findings demonstrate that integrating genomic and functional approaches effectively activates silent BGCs in marine fungi. The fluconazole-associated accumulation and subsequent isolation of cristatumin E, a bioactive indole diketopiperazine dimer, highlight the potential of elicitor-mediated activation to expand the detectable metabolite profile of Aspergillus sp. WHUF0304.
