Genomic insights into the biosynthetic capacity of the sponge-associated fungus Aspergillus puulaauensis Hmp-F48

Marine-derived fungi are prolific producers of structurally diverse secondary metabolites with significant pharmaceutical potential. The discovery of natural products has been unprecedentedly accelerated by the prediction of biosynthetic gene clusters (BGCs) within the whole-genome context. This study presents the whole-genome sequencing, comprehensive annotation, and biosynthetic potential predictions of the sponge-associated fungus Aspergillus puulaauensis Hmp-F48. Genome sequencing of A. puulaauensis Hmp-F48 generated a high-quality draft assembly of 35.86 Mb. Structural annotation revealed a complex genomic architecture, comprising 10,611 protein-coding genes, 210 non-coding RNAs, and 155 tRNAs. Functional annotation using NR, Swiss-Prot, GO, KEGG, and eggNOG databases highlighted significant enrichment in biosynthetic, metabolic, and transport processes. AntiSMASH analysis identified 78 putative BGCs, including 16 type I polyketide synthase (T1PKS), 27 nonribosomal peptide synthetase (NRPS), 7 hybrid PKS-NRPS, 9 terpene-related clusters, 6 RiPP-related clusters and 13 clusters associated with other secondary metabolites. Several clusters exhibited high homology to known BGCs responsible for bioactive secondary metabolites, including asperthecin, sterigmatocystin, calbistrins, F-9775 A/B, nidulanin A, aspercryptins, fellutamide B, acetylaranotin, burnettramic acid A, equisetin, and pyranonigrin E. Experimental isolation confirmed the presence of PKS-derived metabolites, including sterigmatocystin, averantin, and decumbenones — one of which represents a previously undescribed congener. This study highlights the extensive biosynthetic potential of A. puulaauensis Hmp-F48, offering valuable insights into its capacity for secondary metabolite production.