2013
DOI: 10.1371/journal.pgen.1003496
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The Genome of Tolypocladium inflatum: Evolution, Organization, and Expression of the Cyclosporin Biosynthetic Gene Cluster

Abstract: The ascomycete fungus Tolypocladium inflatum, a pathogen of beetle larvae, is best known as the producer of the immunosuppressant drug cyclosporin. The draft genome of T. inflatum strain NRRL 8044 (ATCC 34921), the isolate from which cyclosporin was first isolated, is presented along with comparative analyses of the biosynthesis of cyclosporin and other secondary metabolites in T. inflatum and related taxa. Phylogenomic analyses reveal previously undetected and complex patterns of homology between the nonribos… Show more

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Cited by 143 publications
(139 citation statements)
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“…This topology was supported by strong bootstrap values and indicated that the A domains for each amino acid position from each distantly related fungus were more similar to each other than to the individual A domains from a single given echinocandin-producing strain. This pattern of a one-to-one correspondence between modules and the amino acid specificity of different species is consistent with models of tandem duplication and subfunctionalization prior to divergence from a hypothetical ancestor, as has been hypothesized to occur during the evolution of cyclosporine and peptaibol NRPSs (24,63). Furthermore, within each of these A-domain clades, the branchings of terminal leaves were congruent with the phylogenetic species trees.…”
Section: Phylogenetic Affinities Of the Echinocandin-producing Fungisupporting
confidence: 84%
“…This topology was supported by strong bootstrap values and indicated that the A domains for each amino acid position from each distantly related fungus were more similar to each other than to the individual A domains from a single given echinocandin-producing strain. This pattern of a one-to-one correspondence between modules and the amino acid specificity of different species is consistent with models of tandem duplication and subfunctionalization prior to divergence from a hypothetical ancestor, as has been hypothesized to occur during the evolution of cyclosporine and peptaibol NRPSs (24,63). Furthermore, within each of these A-domain clades, the branchings of terminal leaves were congruent with the phylogenetic species trees.…”
Section: Phylogenetic Affinities Of the Echinocandin-producing Fungisupporting
confidence: 84%
“…The bulk of natural products in clinical use today come from a handful of bacterial and fungal lineages (17)(18)(19)(20)(21). However, genomics studies imply that the ability to make these compounds is much more widespread (22)(23)(24).…”
mentioning
confidence: 99%
“…Analogous 21-module NRPS clusters have been reported from the genomes of Tolypocladium sp. T1 (NP T1 ) (41) and a recently sequenced Tolypocladium inflatum (NP Ti ) (46) (Fig. 4 and SI Appendix, Tables S16 and S18).…”
mentioning
confidence: 99%