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Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates
mSphere, Volume: 5, Issue: 2
Swansea University Author: Claudio Greco
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The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of gr...
American Society for Microbiology
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The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography–high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism.
Aspergillus nidulans, secondary metabolism, intraspecific variation, horizontal gene transfer, viridicatumtoxin
Faculty of Science and Engineering
This project was supported by the U.S. Department of Agriculture, National Institute
of Food and Agriculture (USDA NIFA) postdoctoral fellowship award 2019-67012-29662
to M.T.D. We are also grateful for support from the University of Wisconsin—Madison
Department of Medical Microbiology and Immunology through the Microbial Doctoral
Training Program funded by NIH T32 ES007015 (awarded to M.T.D.) and NIH grant
R01AI065728 to N.P.K. A.R. was supported by a National Science Foundation grant
(DEB-1442113) and a Discovery Grant from Vanderbilt University. T.G. was supported by
a grant from the European Union’s Horizon 2020 research and innovation program
under grant agreement ERC-2016-724173. We thank the Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP), Brazil, for support (grant numbers 2016/
07870-9 and 2017/14159-2 to G.H.G. and L.N.A.R. and 2019/00631-7, 2017/19821-5 to
R.W.B.) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq), Brazil to G.H.G. We also thank the Sao Paulo Research foundation for financial
support awarded to L.N.A.R. (grant 2017/14159-2).