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<p>Myriocin is a fungal secondary metabolite exploited worldwide as a powerful inhibitor of sphingolipid biosynthesis through its structural similarity to sphingosine. We identify the putative myriocin biosynthesis gene cluster (BGC) through de novo sequencing of two producing fungi, <i>Isaria sinclairii</i> and <i>Mycelia sterilia</i>, yielding genomes of 25.2 Mb and 34.2 Mb encoding 27 and 20 secondary metabolite BGCs, respectively. BGCs #5 in <i>I. sinclairii</i> and #18 in <i>M. sterilia</i> both shared and expressed the polyketide synthase (PKS) and alpha oxo-amine synthase (AOS) predicted for myriocin biosynthesis, with 74% and 79% sequence similarity, respectively. Analysis of a 2,236-fungal-genome database suggests the pathway originated in the <i>Sordariomycete</i> ancestor, presenting in two major clades distinguished by PKS gene orientation. The placement of thermophilic <i>M. sterilia</i> suggests myriocin BGC acquisition through horizontal gene transfer, but its origin in <i>I. sinclairii</i> is ambiguous. Heterologously-expressed IsMyrA bound aminomalonate, and a protein-protein docking interface was identified between the acyl carrier protein and IsMyrA. A model of PKS domain function, the roles of the PKS and AOS genes and the synteny of the putative myriocin biosynthetic gene cluster across 34 carrier species of ascomycetes is presented.</p>

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Evolution, structure and function of the putative biosynthetic gene cluster of the fungal secondary metabolite myriocin, a potent inhibitory sphingolipid

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Ben Rutter,
  • Michael A. Herrera,
  • Gustavo Perez Ortiz,
  • Claudio Greco,
  • Ben Ashley,
  • Hai Deng,
  • Abigail Hay,
  • Cameron Bedford,
  • Marius Wenzel,
  • Stephen Mondo,
  • Zachary Konkel,
  • Jason C. Slot,
  • Qinxi Ma,
  • Nicolas Helmstetter,
  • Rhys A. Farrer,
  • Dominic J. Campopiano,
  • Alexandra C. Brand

摘要

Myriocin is a fungal secondary metabolite exploited worldwide as a powerful inhibitor of sphingolipid biosynthesis through its structural similarity to sphingosine. We identify the putative myriocin biosynthesis gene cluster (BGC) through de novo sequencing of two producing fungi, Isaria sinclairii and Mycelia sterilia, yielding genomes of 25.2 Mb and 34.2 Mb encoding 27 and 20 secondary metabolite BGCs, respectively. BGCs #5 in I. sinclairii and #18 in M. sterilia both shared and expressed the polyketide synthase (PKS) and alpha oxo-amine synthase (AOS) predicted for myriocin biosynthesis, with 74% and 79% sequence similarity, respectively. Analysis of a 2,236-fungal-genome database suggests the pathway originated in the Sordariomycete ancestor, presenting in two major clades distinguished by PKS gene orientation. The placement of thermophilic M. sterilia suggests myriocin BGC acquisition through horizontal gene transfer, but its origin in I. sinclairii is ambiguous. Heterologously-expressed IsMyrA bound aminomalonate, and a protein-protein docking interface was identified between the acyl carrier protein and IsMyrA. A model of PKS domain function, the roles of the PKS and AOS genes and the synteny of the putative myriocin biosynthetic gene cluster across 34 carrier species of ascomycetes is presented.