Fungi are an important and prolific source of secondary metabolites (SMs) with diverse chemical structures and a wide array of biological properties. In the past two decades, however, the number of new fungal SMs by traditional monoculture method had been greatly decreasing. Fortunately, a growing number of studies have shown that co-culture strategy is an effective approach to awakening silent SM biosynthetic gene clusters (BGCs) in fungal strains to produce cryptic SMs. To enrich our knowledge of this approach and better exploit fungal biosynthetic potential for new drug discovery, this review comprehensively summarizes all fungal co-culture methods and their derived new SMs as well as bioactivities on the basis of an extensive literature search and data analysis. Future perspective on fungal co-culture study, as well as its interaction mechanism, is supplied.

As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome sequencing and assembly of an endophytic strain Alternaria sp. SPS-2 derived from Echrysantha chrysantha Lindl. and gene annotation using various bioinformatic tools. The results of this study suggested that the genome of strain SPS-2 was 33.4 Mb in size with a GC content of 51% and an N50 scaffold of 2.6 Mb, and 9789 protein-coding genes, including 644 CAZyme-encoding genes, were discovered in strain SPS-2 through KEGG enrichment analysis. The antiSMASH results indicated that strain SPS-2 harbored 22 SM biosynthetic gene clusters (BGCs), 14 of which are cryptic and unknown. LS–MS/MS and GNPS-based analyses suggested that this endophytic fungus is a potential producer of bioactive SMs and merits further exploration and development.