Engineering of nicotianamine synthesis enhances cadmium mobility in plants and results in higher seed cadmium concentrations.

Efficient biofortification, i.e., the enrichment of edible plant organs with micronutrients available for human consumption, is pursued through breeding and genetic engineering approaches. Enriching for iron (Fe) and zinc (Zn), two of the most critical trace elements, in cereal grains can be achieved by boosting the synthesis of nicotianamine (NA), a key metal chelator in plants. However, metal transport and distribution pathways are not entirely specific and may lead to the adventitious accumulation of potentially highly toxic non-essential metals such as cadmium (Cd). We found evidence for the formation of intracellular Cd-NA complexes driving Cd uptake and accumulation in two different yeast species and therefore studied Arabidopsis thaliana mutants as well as NA synthase overexpression lines in wild-type and mutant backgrounds that showed varying degrees of NA deficiency or overproduction relative to controls. NA synthesis was enhanced by metal excess and conferred Cd and Zn tolerance. Importantly, when cultivated on soil containing environmentally relevant Cd levels, NA-overproducing lines accumulated not only more Fe and Zn in their seeds but also more Cd. Thus, the engineering of NA synthesis can result in an unintended food safety risk that should be mitigated by carefully monitoring Cd phytoavailability in soils and, ideally, the use of low Cd germplasm for the engineering of biofortified crops.