Acrophiarin (antibiotic S31794/F-1) from Penicillium arenicola shares biosynthetic features with both Aspergillus- and Leotiomycete-type echinocandins

Nan Lan, Bruno Perlatti, Daniel J. Kvitek, Philipp Wiemann, Colin J. B. Harvey, Jens Christian Frisvad, Zhiqiang An, Gerald F. Bills*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The antifungal echinocandin lipopeptide, acrophiarin, was circumscribed in a patent in 1979. We confirmed that the producing strain NRRL 8095 is Penicillium arenicola and other strains of P. arenicola produced acrophiarin and acrophiarin analogues. Genome-sequencing of NRRL 8095 identified the acrophiarin gene cluster. Penicillium arenicola and echinocandin-producing Aspergillus species belong to the family Aspergillaceae of the Eurotiomycetes, but several features of acrophiarin and its gene cluster suggest a closer relationship with echinocandins from Leotiomycete fungi. These features include hydroxy-glutamine in the peptide core instead of a serine or threonine residue, the inclusion of a non-heme iron, α-ketoglutarate-dependent oxygenase for hydroxylation of the C3 of the glutamine, and a thioesterase. In addition, Penicillium arenicola bears similarity to Leotiomycete echinocandin-producing species because it exhibits selfresistance to exogenous echinocandins. Phylogenetic analysis of the genes of the echinocandin biosynthetic family indicated that most of the predicted proteins of acrophiarin gene cluster exhibited higher similarity to the predicted proteins of the pneumocandin gene cluster of the Leotiomycete Glarea lozoyensis than to those of the echinocandin B gene cluster from A. pachycristatus. The fellutamide gene cluster and related gene clusters are recognized as relatives of the echinocandins. Inclusion of the acrophiarin gene cluster into a comprehenisve phylogenetic analysis of echinocandin gene clusters indicates the divergent evolutionary lineages of echinocandin gene clusters are descendents from a common ancestral progenitor. The minimal ten-gene cluster may have undergone multiple gene acquisitions or losses and possibly horizontal gene transfer after the ancestral separation of the two lineages.
Original languageEnglish
JournalEnvironmental Microbiology
ISSN1462-2912
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Antifungal
  • Ascomycota
  • Aspergillaceae
  • Fellutamides
  • Fermentation
  • Horizonal gene transfer
  • Nonribosomal peptide synthease
  • Phialomyces
  • Secondary metabolites

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