This study demonstrates that pathogenic Fusarium species possess functional methylcitrate cycles for detoxifying propionyl-CoA, a toxic metabolite generated during degradation of certain carbon sources. The researchers identified and characterized methylcitrate synthase genes from two species: Fusarium solani and Fusarium verticillioides. Although the enzymes shared 96% amino acid sequence identity, they exhibited distinct biochemical properties. F. solani efficiently utilized propionate as a carbon source and showed strong methylcitrate synthase activity during growth on this substrate, reflecting its saprophytic soil lifestyle. In contrast, F. verticillioides grew poorly on propionate but displayed higher citrate synthase activity and greater thermal stability. These biochemical differences correlated with observable growth differences between species on propionyl-CoA-generating carbon sources. The findings suggest that differential adaptation of methylcitrate cycle enzymes contributes to the distinct ecological niches and pathogenic strategies of these Fusarium species—F. solani as a soil saprophyte and human pathogen, and F. verticillioides as a plant pathogen. Understanding this pathway may inform development of novel antifungal strategies, particularly relevant since propionyl-CoA accumulation inhibits both primary and secondary metabolism including mycotoxin production.

Key findings

• F. solani and F. verticillioides both possess functional methylcitrate cycles, confirmed through enzyme identification and biochemical characterization of purified methylcitrate synthases from both species.
• Despite 96% amino acid sequence identity, the two methylcitrate synthases displayed different biochemical properties: F. verticillioides enzyme had higher citrate synthase activity and greater thermal stability than F. solani enzyme.
• F. solani efficiently utilized propionate and showed strong methylcitrate synthase activity during growth on this carbon source, while F. verticillioides grew poorly on propionate with lower enzyme activity, reflecting their different ecological lifestyles.
• Biochemical differences in methylcitrate synthase correlate with differential growth abilities on propionyl-CoA-generating substrates between the two species.