Genome Assembly and Genetic Traits of the Pleuromutilin-Producer Clitopilus passeckerianus DSM1602

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thomas Schafhauser - , Eberhard Karls Universität Tübingen (Autor:in)
  • Daniel Wibberg - , Universität Bielefeld, Forschungszentrum Jülich (Autor:in)
  • Antonia Binder - , Professur für Allgemeine Mikrobiologie, Eberhard Karls Universität Tübingen (Autor:in)
  • Christian Rückert - , Universität Bielefeld (Autor:in)
  • Tobias Busche - , Universität Bielefeld (Autor:in)
  • Wolfgang Wohlleben - , Eberhard Karls Universität Tübingen, Deutsche Zentrum für Infektionsforschung (Autor:in)
  • Jörn Kalinowski - , Universität Bielefeld (Autor:in)

Abstract

The gilled mushroom Clitopilus passeckerianus (Entolomataceae, Agaricales, Basidiomycota) is well known to produce the terpenoid pleuromutilin, which is the biotechnological basis for medically important antibiotics such as lefamulin and retapamulin. Their unique mode of action and good tolerance entails an increasing demand of pleuromutilin-derived antibiotics in veterinary and human health care. Surprisingly, despite their pharmaceutical importance, no genome sequence is available of any pleuromutilin-producing fungus. Here, we present the high-quality draft genome sequence of the pleuromutilin-producer C. passeckerianus DSM1602 including functional genome annotation. More precisely, we employed a hybrid assembly strategy combining Illumina sequencing and Nanopore sequencing to assemble the mitochondrial genome as well as the nuclear genome. In accordance with the dikaryotic state of the fungus, the nuclear genome has a diploid character. Interestingly, the mitochondrial genome appears duplicated. Bioinformatic analysis revealed a versatile secondary metabolism with an emphasis on terpenoid biosynthetic enzymes in C. passeckerianus and also in related strains. Two alleles of biosynthetic gene clusters for pleuromutilin were found in the genome of C. passeckerianus. The pleuromutilin genes were reassembled with yeast-specific elements for heterologous expression in Saccharomyces cerevisiae. Our work lays the foundation for metabolic strain engineering towards higher yields of the valuable compound pleuromutilin.

Details

OriginalspracheEnglisch
Aufsatznummer862
FachzeitschriftJournal of Fungi
Jahrgang8
Ausgabenummer8
PublikationsstatusVeröffentlicht - Aug. 2022
Peer-Review-StatusJa

Schlagworte

Schlagwörter

  • Agaricales, biosynthetic gene cluster, Clitopilus, genome assembly, heteroplasmic mycelium, Illumina sequencing, mitochondrial genome, Nanopore sequencing, pleuromutilin, terpene synthase