Filamentous fungi are one of the major sources of natural products (NPs;which are also termed as secondary metabolites (SMs)) with diverse biological activities,which have been widely used in agriculture,industry,and pharmaceuticals.Fungi are the second largest species in nature,and their biodiversity implies genomic diversity,which,in turn,predicts the structural diversity of metabolites.In general,NPs can be classified as polyketides (PKs),nonribosomal peptides (NRPs),hybrid PK-NRPs,or terpenoids according to the types of their biosynthetic skeleton enzymes.These enzymes include polyketide synthases (PKSs),nonribosomal peptide synthetases (NRPSs),hybrid polyketide synthasenonribosomal peptide synthetases (PKS-NRPSs),and terpene synthases or terpene cyclases (TCs).A hallmark in fungal NP biosynthesis is that the relevant genes are usually arranged close to each other on the chromosome in what is called a biosynthetic gene cluster (BGC).Over 2,200 fungal genome sequences are publicly available because of the rapid development of genome sequencing technology and the launch of 1000 Fungal Genome Project by the Joint Genome Institute (JGI).Bioinformatics analyses confirm that the fungal genome has an abundance of BGCs.An NP “dark matter” treasure may be present in the fungal genome as over 90% of BGCs are unexplored,silent,or cryptic (He et al.,2018;Keller,2019).These data provide us an opportunity to search for fungal NPs using gene/genome as the starting point.
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