Interspecies Genomic Variation and Transcriptional Activeness of Secondary Metabolism-Related Genes in Aspergillus Section Fumigati

Hiroki Takahashi; Maiko Umemura; Akihiro Ninomiya; Yoko Kusuya; Masaaki Shimizu; Syun-Ichi Urayama; Akira Watanabe; Katsuhiko Kamei; Takashi Yaguchi; Daisuke Hagiwara

doi:10.3389/ffunb.2021.656751

Interspecies Genomic Variation and Transcriptional Activeness of Secondary Metabolism-Related Genes in Aspergillus Section Fumigati

Front Fungal Biol. 2021 Apr 16:2:656751. doi: 10.3389/ffunb.2021.656751. eCollection 2021.

Authors

Hiroki Takahashi^{1

2

3}, Maiko Umemura⁴, Akihiro Ninomiya⁵, Yoko Kusuya¹, Masaaki Shimizu⁶, Syun-Ichi Urayama^{5

7}, Akira Watanabe¹, Katsuhiko Kamei¹, Takashi Yaguchi¹, Daisuke Hagiwara^{1

5

7}

Affiliations

¹ Medical Mycology Research Center, Chiba University, Chiba, Japan.
² Molecular Chirality Research Center, Chiba University, Chiba, Japan.
³ Plant Molecular Science Center, Chiba University, Chiba, Japan.
⁴ Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
⁵ Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
⁶ Department of Biology, Faculty of Science, Chiba University, Chiba, Japan.
⁷ Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Japan.

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.

Keywords: Aspergillus fumigatus; Aspergillus section Fumigati; comparative genomic analysis; comparative transcriptomic analysis; gliotoxin; secondary metabolic gene; terrein; viriditoxin.