Uncovering the Biochemical Origin of the Causative Agents of Favism in Faba Bean

Faba bean (Vicia faba L.) is a widely adapted and high-yielding legume crop cultivated for its protein-rich seeds [1]. However, the seeds accumulate the pyrimidine glucosides vicine and convicine, which can cause haemolytic anaemia (favism) in 400 million genetically predisposed individuals [2]. Here, I will present our collaborative work aimed at uncovering the biochemical origin of these anti-nutrients, which was recently published in Nature Plants [3]. By using gene-to-metabolite correlations, gene mapping and genetic complementation, we identified a key enzyme in vicine and convicine biosynthesis, VC1. We showed that VC1 has GTP cyclohydrolase II activity and that the purine GTP is a precursor of both vicine and convicine. Finally, we demonstrated that cultivars with low vicine and convicine levels carry an inactivating insertion in the coding sequence of VC1. Our results reveal an unexpected, purine rather than pyrimidine, biosynthetic origin for vicine and convicine and pave the way for the development of faba bean cultivars that are completely free of these anti-nutrients.

[1] Duc, G. et al. in Handbook of Plant Breeding: Grain Legumes Vol. 10 (ed. De Ron, A.) Ch. 5 (Springer, 2015).

[2] Luzzatto, L. & Arese, P. Favism and glucose-6-phosphate dehydrogenase deficiency. N. Engl. J. Med. 378, 1068–1069 (2018).

[3] Björnsdotter, E. et al. VC1 catalyses a key step in the biosynthesis of vicine in faba bean. Nature Plants 7, 923-931 (2021).