Structure of the host-specific toxins produced by the fungal pathogen Periconia circinata.

Abstract

Four metabolites named peritoxins A and B and periconins A and B have been isolated together with the known metabolite circinatin from culture filtrates of the fungal pathogen Periconia circinata. Peritoxins A and B, which correspond to the P. circinata toxins Ia and Ha partially characterized in previous work, are selectively toxic to genotypes of Sorghum bicolor susceptible to the pathogen, whereas periconins A and B are biologically inactive. Combination of instrumental analysis and chemical degradation has led to structural assignments for each of the four compounds; only the configuration at some of the chiral centers remains undefined. Structural comparison suggests a precursor role for circinatin in the formation of the peritoxins and the periconins.The soil-borne fungus Periconia circinata (Mangin) Sacc. causes milo disease, a root and crown rot of the grain sorghum Sorghum bicolor (L.) (1). Early studies by Leukel (2) identified P. circinata as the causal agent and suggested that a toxic metabolite was involved in the milo disease syndrome. Scheffer and Pringle (3) established that only pathogenic isolates of the fungus produce a toxin with activity against sorghum and documented its involvement in disease symptom development. The toxin, designated PC toxin, elicits the disease symptoms in genotypes of sorghum that are susceptible to the pathogen, and toxin production is essential for pathogenicity of the fungus. Thus, PC toxin is one of a group of phytotoxic metabolites known as hostspecific toxins (4). Because milo disease is controlled by resistant genotypes with the homozygous recessive alleles at the pc locus (5), P. circinata no longer poses a threat to sorghum production. However, this host-pathogen interaction affords several advantages in biochemical and molecular studies of disease development: near-isogenic resistant (pcpc) and susceptible (PcPc) genotypes of sorghum are available (5), several reliable bioassays for toxin activity have been developed (6), and two preparations with toxic activity have been isolated and partially characterized (7). Therefore, the determinative events of the host-pathogen interaction can be reduced to the interaction of the toxin with a single gene-determined site or product.In a previous paper (8) it was shown that when the fungus was grown under conditions that suppressed toxin production it accumulated a nontoxic compound, circinatin (structure 1), ¶ which was suspected to act as a biosynthetic precursor of the unknown toxins.Analysis of culture filtrates obtained under conditions known to maximize toxin production (7) has now yielded, in addition to circinatin, two toxic compounds, the peritoxins A and B, and two biologically inactive congeners, the periconins A and B. Here we provide evidence that establishes 2-5 as the structures of the four metabolites; these structures are in keeping with the hypothesis oftheir filiation from circinatin (1) as a common precursor. MATERIALS AND METHODSA toxin-producing strain of P. circinata was grown for 21 days ...

Differential Synthesis of Peritoxins and Precursors by Pathogenic Strains of the Fungus Periconia circinata

“…Culture fluids containing metabolites produced by the Tox ϩ and Tox Ϫ strains were tested for their genotype-specific phytotoxicity against intact seedlings or excised leaves and by root growth inhibition and electrolyte leakage bioassays as described previously (6,7,8,9,16,19). In the bioassays and the pathogenicity tests, near-isogenic cultivars 'Colby' (Pc Pc) and 'Resistant Colby' (pc pc) were used as the toxin-sensitive, susceptible genotype and toxin-insensitive, resistant genotype, respectively (21).…”

“…In all bioassays performed in this study (Table 1), as well as in experiments with over 50 isolates conducted during the past 25 years (6,7,8,9,15,16,19,26,27; data not shown), only Tox ϩ strains were pathogenic. No ex- ceptions have been observed to the conclusion that pathogenicity of P. circinata, i.e., the ability to cause root rot and associated disease symptoms beyond small, restricted cortical lesions on the root, absolutely requires the ability to produce peritoxins.…”

“…Peritoxins exhibit host-selective toxicity at concentrations as low as 1 ng ml Ϫ1 against sorghum genotypes that are susceptible to the pathogen (16,26). Treatment of sorghum seedlings with culture filtrates or purified preparations of toxin reproduces the biochemical and visible symptoms of the disease in a genotypespecific manner (6,7,9,23,27).…”

“…Pathogenic strains of P. circinata produce peritoxins, which are low-molecular-weight, hybrid molecules consisting of a peptide and a chlorinated polyketide (2,16). Peritoxins exhibit host-selective toxicity at concentrations as low as 1 ng ml Ϫ1 against sorghum genotypes that are susceptible to the pathogen (16,26).…”

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

“…The peritoxins are low-molecular weight, hybrid molecules consisting of a peptide and chlorinated polyketide. (Churchill et al, 2001;Macko et al, 1992 (Jiao, 2006). Depsipeptide β-Dglucosyl-hydroxydestruxin B was produced by a fungus, Alternaria alternata f. sp.…”