Structural Studies of Aliphatic Glucosinolate Chain-Elongation Enzymes

Plants evolved specialized metabolic pathways through gene duplication and functional divergence of enzymes involved in primary metabolism. The results of this process are varied pathways that produce an array of natural products useful to both plants and humans. In plants, glucosinolates are a diverse class of natural products. Glucosinolate function stems from their hydrolysis products, which are responsible for the strong flavors of Brassicales plants, such as mustard, and serve as plant defense molecules by repelling insects, fighting fungal infections, and discouraging herbivory. Additionally, certain hydrolysis products such as isothiocyanates can potentially serve as cancer prevention agents in humans. The breadth of glucosinolate function is a result of its great structural diversity, which comes from the use of aliphatic, aromatic and indole amino acids as precursors and elongation of some side chains by up to nine carbons, which, after the formation of the core glucosinolate structure, can undergo further chemical modifications. Aliphatic methionine-derived glucosinolates are the most abundant form of these compounds. Although both elongation and chemical modification of amino acid side chains are important for aliphatic glucosinolate diversity, its elongation process has not been well described at the molecular level. Here, we summarize new insights on the iterative chain-elongation enzymes methylthioalkylmalate synthase (MAMS) and isopropylmalate dehydrogenase (IPMDH).