Folate Biofortification of Potato by Tuber-Specific Expression of Four Folate Biosynthesis Genes

Insufficient dietary intake of micronutrients, known as "hidden hunger", is a devastating global burden, affecting two billion people. Deficiency of folates (vitamin B9), which are known to play a central role in C₁ metabolism, causes birth defects in at least a quarter million people annually. Biofortification to enhance the level of naturally occurring folates in crop plants, proves to be an efficient and cost-effective tool in fighting folate deficiency. Previously, introduction of folate biosynthesis genes GTPCHI and ADCS, proven to be a successful biofortification strategy in rice and tomato, turned out to be insufficient to adequately increase folate levels in potato tubers. Here, we provide a proof of concept that additional introduction of HPPK/DHPS and/or FPGS, downstream genes in mitochondrial folate biosynthesis, enables augmentation of folates to satisfactory levels (12-fold) and ensures folate stability upon long-term storage of tubers. In conclusion, this engineering strategy can serve as a model in the creation of folate-accumulating potato cultivars, readily applicable in potato-consuming populations suffering from folate deficiency.