Structure, Reactivity, and Chemistry of Fluoroalkyl Radicals.

Sirodesmin PL is a phytotoxin produced by the fungus Leptosphaeria maculans, which causes blackleg disease of canola (Brassica napus). This phytotoxin belongs to the epipolythiodioxopiperazine (ETP) class of toxins produced by fungi including mammalian and plant pathogens. We report the cloning of a cluster of genes with predicted roles in the biosynthesis of sirodesmin PL and show via gene disruption that one of these genes (encoding a two-module non-ribosomal peptide synthetase) is essential for sirodesmin PL biosynthesis. Of the nine genes in the cluster tested, all are co-regulated with the production of sirodesmin PL in culture. A similar cluster is present in the genome of the opportunistic human pathogen Aspergillus fumigatus and is most likely responsible for the production of gliotoxin, which is also an ETP. Homologues of the genes in the cluster were also identified in expressed sequence tags of the ETP producing fungus Chaetomium globosum. Two other fungi with publicly available genome sequences, Magnaporthe grisea and Fusarium graminearum, had similar gene clusters. A comparative analysis of all four clusters is presented. This is the first report of the genes responsible for the biosynthesis of an ETP.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2958.2004.04215.x

The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus Leptosphaeria maculans.

Gliotoxin is a secondary metabolite produced by several fungi including the opportunistic animal pathogen Aspergillus fumigatus It is a member of the epipolythiodioxopiperazine (ETP) class of toxins characterised by a disulphide bridged cyclic dipeptide A putative cluster of 12 genes involved in gliotoxin biosynthesis has been identified in A fumigatus by a comparative genomics approach based on homology to genes from the sirodesmin (another ETP) biosynthetic gene cluster of Leptosphaeria maculans The physical limits of the cluster in A fumigatus have been defined by bioinformatics and by identifying the genes that are co-regulated and whose timing of expression correlates with the production of gliotoxin in culture

Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus

From glucose to aromatics: recent developments in natural products of the shikimic acid pathway

When cultured in vitro, Aspergillus fumigatus generated a metabolite(s) with anti-phagocytic activity as tested by macrophage adherence to plastic and phagocytosis of particulate matter. The metabolite(s) appeared after 3 d culture and reached a peak concentration after 5-6 d. The action of the anti-phagocytic agent(s) was rapid (5-15 min) and appeared not to alter membrane permeability or cause rapid cell death. Treatment of stimulator spleen cells with the agent(s) inhibited their ability to induce alloreactive and major histocompatibility complex restricted cytotoxic T cells. The metabolite(s) was chloroform-soluble and separated into three biologically active compounds on thin-layer chromatography. These compounds were purified > 1000-fold and one of them was identified as gliotoxin, a known metabolite of A. fumigatus, based upon NMR and IR spectroscopy, mass spectrometry, biological properties and other data.

K. G. Das

Papers

Biosynthetic studies on gliotoxin using stable isotopes and mass spectral methods.

Mass Spectral Studies. III. Fragmentation of Aromatic Amides

Mass spectral studies. ii. molecular rearrangement under electron impact

Fluoro Compounds. II.1 Reactions and Nuclear Magnetic Resonance Studies of Some Fluorobromo Esters

Terpenoids—LXXXVI : Structure of epi-ψ-taraxastanonol and epi-ψ-taraxastanediol☆