Abstract
Filamentous fungi produce various bioactive compounds that are biosynthesized by sets of proteins encoded in biosynthesis gene clusters (BGCs). For an unknown reason, many BGCs are transcriptionally silent in laboratory conditions, which has hampered the discovery of novel fungal compounds. The transcriptional reactiveness of fungal secondary metabolism is not fully understood. To gain the comprehensive view, we conducted comparative genomic and transcriptomic analyses of nine closely-related species of Aspergillus section Fumigati (A. fumigatus, A. fumigatiaffinis, A. novofumigatus, A. thermomutatus, A. viridinutans, A. pseudoviridinutans, A. lentulus, A. udagawae, and Neosartorya fischeri). For expanding our knowledge, we newly sequenced genomes of A. viridinutans and A. pseudoviridinutans, and reassembled and reannotated the previously released genomes of A. lentulus and A. udagawae. Between 34 and 84 secondary metabolite (SM) backbone genes were identified in the genomes of these nine respective species, with 8.7-51.2% being unique to the species. A total of 247 SM backbone gene types were identified in the nine fungi. Ten BGCs are shared by all nine species. Transcriptomic analysis using A. fumigatus, A. lentulus, A. udagawae, A. viridinutans, and N. fischeri was conducted to compare expression levels of all SM backbone genes in four different culture conditions; 32-83% of SM backbone genes in these species were not expressed in the tested conditions, which reconfirmed that large part of fungal SM genes are hard to be expressed. The species-unique SM genes of the five species were expressed with lower frequency (18.8% in total) than the SM genes that are conserved in all five species (56%). These results suggest that the expression tendency of BGCs is correlated with their interspecies distribution pattern. Our findings increase understanding of the evolutionary processes associated with the regulation of fungal secondary metabolism.
Highlights
Filamentous fungi produce various small molecules known as secondary metabolites (SMs; called natural products) that are thought to contribute to their survival in environmental niches (Keller, 2015; Künzler, 2018)
Our genomic study provides a comprehensive catalog of SM backbone genes in A. lentulus, A. udagawae, A. viridinutans, A. pseudoviridinutans, A. fumigatiaffinis, A. novofumigatus, and A. thermomutatus, whereas those of A. fumigatus and N. fischeri have been well-investigated previously
A. fumigatus was estimated to have the largest number of characterized SM gene clusters among fungi even though the number of signature genes predicted by antiSMASH or other research was relatively small (∼34 genes) (Sanchez et al, 2012; Mead et al, 2019)
Summary
Filamentous fungi produce various small molecules known as secondary metabolites (SMs; called natural products) that are thought to contribute to their survival in environmental niches (Keller, 2015; Künzler, 2018). Genes encoding backbone-producing and tailoring enzymes, transcriptional regulators, and efflux pumps are often arrayed in a biosynthesis gene cluster (BGC). Fungi, including phytopathogens and human pathogens, possess large numbers of SM-producing gene clusters in their genomes, which indicates an ability to produce myriad metabolites that could be used to impact humans (Sanchez et al, 2012; Hansen et al, 2015; Nielsen et al, 2017; Vesth et al, 2018; Kjærbølling et al, 2020). One explanation for the low expression of SM-related genes in laboratory-controlled conditions is that unknown ecological cues trigger fungal SM production but cannot be reproduced in the laboratory. The molecular mechanisms underlying artificial activation of SM-related genes remain to be investigated
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