Folate synthesis and metabolism in plants and prospects for biofortification

Folates are essential cofactors for one-carbon transfer reactions in most living organisms and are required for the biosynthesis of nucleic acids, amino acids, and pantothenate. Unlike plants and microorganisms, humans cannot synthesize folates de novo and must acquire them from the diet, primarily from plant foods. However, lack of folates is the most common vitamin deficiency in the world and has serious health consequences, including increased risk of neural tube defects in infants, cancers, and vascular diseases. Consequently, there is much interest in engineering plants with enhanced folate content (biofortification). In this review, we outline progress in defining the plant folate synthesis pathway and its unique compartmentation and point out sectors of folate metabolism that have yet to be elucidated, including transport and catabolism. We also consider possible strategies to enhance plant folate synthesis and accumulation by metabolic engineering.