10.1021/acs.orglett.1c00206
The study investigates the enzymatic basis for quinine biosynthesis, focusing on the early and late steps of the pathway. Quinine, an alkaloid produced by Cinchona trees, is historically used as an antimalarial drug and as a flavor ingredient in beverages. The researchers combined metabolomics and transcriptomics data from different tissues of Cinchona pubescens to identify genes involved in quinine biosynthesis. They discovered three key enzymes: a medium-chain alcohol dehydrogenase (CpDCS), an esterase (CpDCE), and an O-methyltransferase (CpOMT1). CpDCS and CpDCE were involved in converting strictosidine aglycone to dihydrocorynantheal, an intermediate in quinine biosynthesis, through reduction and esterase-triggered decarboxylation. CpOMT1 was found to specifically act on 6′-hydroxycinchoninone, suggesting a preferred order for the late steps of quinine biosynthesis. The chemicals used in the study included strictosidine, corynantheine aldehyde, dihydrocorynantheine aldehyde, and cinchoninone, among others, which served as substrates, intermediates, and products in the biosynthetic pathway of quinine. The purpose of these chemicals was to elucidate the enzymatic steps and intermediates involved in the biosynthesis of quinine, providing insights into the metabolic pathways and potential for synthetic biology applications in quinine production.
