Modern Strategies for the Diversification of the Supply of Natural Compounds: The Case of Alkaloid Painkillers.

Plant-derived natural compounds have been used for treating diseases since prehistorical times. The supply of many plant-derived natural compounds for medicinal purposes, such as thebaine, morphine, and codeine, is primarily dependent on opium poppy crop harvesting. This dependency adds an extra risk factor to ensuring the supply chain because crops are highly susceptible to environmental conditions. Emerging technologies, such as biocatalysis, might help to solve this problem by diversifying the sources of supply of these compounds. Here we review the first committed step in the production of alkaloid painkillers, the production of S-norcoclaurine, and the enzymes involved. The improvement of these enzymes can be carried out experimentally by directed evolution and rational design strategies, supported by computational methods, to create variants that produce the S-norcoclaurine precursor for alkaloid painkillers in heterologous organisms, meeting the pharmaceutical industry standards and needs without depending on opium poppy crops.