Fumaric acid is used extensively in the food, medicine, and polymer industries because of its reductive ability and nontoxic nature, and it is primarily produced by the isomerization of the geometric isomer, maleic acid, by ~300,000 metric tons annually. In industry, acids such as aqueous hydrochloric acid as well as thiourea have been used as catalysts for the isomerization reaction, but extensive heating is inevitable for expediting the reactions to proceed at satisfactory rates. For the chemical conversion under benign reaction conditions, natural production of fumaric acid is achieved by fermentation with maleate isomerase (EC 5.2.1.1), also known as maleate cis-trans isomerase. This enzyme, which is a member of the Asp/Glu racemase superfamily discovered in bacteria, catalyzes the industrially useful isomerization reaction under ambient conditions. Structural analysis and mutational studies of the enzymes revealed that thiols play a crucial role in the reaction. As such, thiol-based molecules have been investigated as promoters of cis-trans isomerization of unsaturated hydrocarbons; however, none of them was genuinely catalytic conducive to practical applications (Table ). Indeed, Chatgilialoglu and co-workers found the combination of 2-mercaptoethanol and 60 Co γ-radiolysis led to catalytic cis-trans isomerization of monounsaturated fatty acids, but the use of organic solvents may hinder efficient conversion. Adducts of thiols to double bonds by nucleophilic addition are frequently encountered as stable products, while the subsequent elimination of thiols following the pseudo-E/Z isomerization is impeded by both kinetics and thermodynamics.