Structure revision of cryptosporioptides and determination of the genetic basis for dimeric xanthone biosynthesis in fungi

Claudio Greco, Kate de Mattos-Shipley, Andrew M Bailey, Nicholas P Mulholland, Jason L Vincent, Christine L Willis, Russell J Cox, Thomas J Simpson

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
173 Downloads (Pure)

Abstract

Three novel dimeric xanthones, cryptosporioptides A-C were isolated from Cryptosporiopsis sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of Cryptosporiopsis sp. 8999 was sequenced and the dimeric xanthone (dmx) biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene (dmxR5) encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of dmxR5 led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, e.g. the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.

Original languageEnglish
Pages (from-to)2930-2939
Number of pages10
JournalChemical Science
Volume10
Issue number10
Early online date21 Jan 2019
DOIs
Publication statusPublished - 14 Mar 2019

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

Keywords

  • Synthetic Biology

Fingerprint Dive into the research topics of 'Structure revision of cryptosporioptides and determination of the genetic basis for dimeric xanthone biosynthesis in fungi'. Together they form a unique fingerprint.

Cite this