Structural diversity and biosynthesis of plant derived p-menthane monoterpenes

Abstract

p-Menthanes are among the most valuable groups of monoterpenoids produced by plants. Products such as menthol, carvone, pulegone, and limonene are well-known fragrance compounds that are also used as pesticides or medicines. In flowering plants, they are synthesized and stored in specialized anatomical structures such as glandular trichomes (GT), secretory cavities, and root resin ducts. These metabolites originate through the 2C-methyl-d-erythritol-4-phosphate precursor pathway in the plastids of GT secretory cells but also require the activity of prenyltransferases and modifying enzymes in the mitochondria and endoplasmic reticulum to complete their functionalization to biologically active forms. (−)-Menthol is the best characterized of these and is pharmacologically active due to its affinity for the Cold and Menthol Receptor 1 and the κ-Opioid Receptor. p-Menthanes are found throughout the plant kingdom, and although their essential oils are still obtained mostly through traditional agriculture, synthetic biology approaches increasingly enable large scale production of economically valuable examples in microbes and cell free systems. Limonene is the model p-menthane monoterpene, and detailed studies of (+)-limonene synthase and (−)-limonene synthase crystal structures have enabled identification of catalytic residues and determinants of stereospecificity, which has implications for the ecological properties of these volatile products in defense and interspecific signaling. This review examines the chemical diversity of the p-menthanes in the plant kingdom, their biosynthetic origins in specialized anatomical structures, and the enzymology of p-menthane biosynthetic enzymes from diverse plant families.