A candidate gene cluster for the biosynthesis of diplodiatoxin

Background

Stenocarpella maydis is a necrotrophic fungus, member of the Diaporthales family (Ascomycetes, Sordariomycetes), that causes diplodia ear rot, an economically important disease of maize. S. maydis is known to be the causative agent of diplodiosis, a neuromycotoxicosis of livestock that feed on maize infected with this pathogen. Although S. maydis is commonly found wherever maize is grown, diplodiosis has been of particular concern in South Africa, where it is predominantly reported. In field conditions, symptoms of diplodiosis in animals become visible from one to two weeks after exposure, when affected animals typically have their back arched, and show abnormal salivation and lacrimation. For over 100 years there is a clear consensus that diplodiosis is caused by S. maydis. However, to this day the specific mycotoxin that induces diplodiosis is currently unknown. Several metabolites have already been isolated from S. maydis, including diplodiatoxin, diplonine, diplosporin, dipmatol, and chaetoglobosins K, L, M and O. But none of these metabolites have conclusively been responsible to cause diplodiosis. In part, this is due to a lack of studies aiming to induce the disease by administering these purified metabolites to cattle and sheep. As a result, diplodiosis is considered the only major mycotoxicosis for which the responsible metabolite(s) is still elusive.

Major findings

Interestingly, the molecular structure of diplodiatoxin is similar to that of betaenone B, produced by Phoma betae, a fungal pathogen that causes leaf spot and root rot diseases in sugar beet. The gene cluster for betaenone B biosynthesis (bet) contains eight genes (bet1-4, ORF1-4), one of which (bet1) encodes a highly-reducing polyketide synthase as the key enzyme for betaenone B biosynthesis. The similarity of the molecular structure of diplodiatoxin and betaenone B raises the possibility that they are produced by homologous gene clusters. Indeed, I identified a gene cluster homologous to the bet cluster in the genome of S. maydis, and pointed out that this gene cluster is likely involved in diplodiatoxin biosynthesis.

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Check out this article Zaccaron et al. 2017 and this essay.