Nutritional‐rich and stress‐tolerant crops by saccharopine pathway manipulation

Abstract Lysine is a limiting essential amino acid in cereals, a major food source for humans and animals. Although cereals can synthesize lysine from aspartate, the pathway is feedback regulated in a manner that restricts lysine accumulation. Another step that restricts lysine accumulation in seeds is the saccharopine pathway for lysine catabolism. This pathway converts lysine to α ‐aminoadipic‐ δ ‐semialdehyde ( AASA ) by the bifunctional enzyme lysine‐ketoglutarate reductase/saccharopine dehydrogenase ( LKR / SDH ). Then, AASA is converted to aminoadipic acid ( AAA ) by α ‐aminoadipic‐ δ ‐semialdehyde dehydrogenase ( AASADH ). The downregulation of LKR / SDH in seeds results in the overaccumulation of free lysine to levels that meet human nutritional requirements. However, the saccharopine pathway is also involved in stress response in plants, animals, and bacteria. In these organisms, the gene encoding LKR / SDH is upregulated under osmotic, salt, and oxidative stress conditions. The role of the saccharopine pathway in stress response is not well understood, but the overexpression of AASADH results in stress‐tolerant plants and animal cells. The saccharopine pathway may thus act either by producing osmolytes, such as pipecolic acid and proline, or by signaling compounds that regulate stress‐response genes. In this review, we discuss the potential use of the saccharopine pathway to engineer nutritional‐rich and stress‐tolerant crops.