Research Reveals Sustainable Method to Produce Opiate Antidotes That Save Lives at Lower Cost

The overdose of opiates has exploded. According to the National Center for Health Statistics, an average of 130 Americans die each day from an overdose of opioids.1 The high cost of antidotes like NARCAN prevents many first responders from gaining access to life-saving antidotes when they need it most.2 Donald Danforth Plant Science Center has identified a new method of producing these compounds with the help of a microorganism discovered in a waste stream badociated with poppy processing at opium. This green chemistry process has the potential to dramatically reduce the cost of antidote drugs as well as reduce the currently used chemicals that produce large amounts of harmful waste. The details of the discovery were published on the cover in the newspaper. Nature's sustainability: "Morphinan N-demethylase enzyme for a more durable treatment of opiates".

"Enzymes perform reactions at higher yields than synthetic chemistry, thus reducing the cost and impact of drug production on the environment." We are now working on optimizing Enzyme production levels on a scale sufficient for industrial processes A greener manufacturing would make a vital difference, "said Megan Augustin, senior author and research badociate at Kutchan Lab at the Danforth Center.

Natural opiates, such as morphine and thebaine, are produced in poppy species. Thebaine is converted into badgesics and opioid dependence treatments, the latter requiring a chemical reaction called N-demethylation. Current opioid N-demethylation uses harmful reagents, resulting in harmful wastes. One way to make opiate production more sustainable is to use enzymes rather than chemicals. Microorganisms are a rich source of enzymes that are useful for metabolizing unique compounds in their environment. Augustin and his colleagues surveyed a sample of opium processing operations to identify an organism capable of catalyzing N-demethylation of opiates. To identify a biocatalyst, a sludge sample was subjected to minimal medium containing thebaine as the only carbon source. This led to the discovery of Thebainfresser, a methylobacterium that metabolizes opiates by eliminating the N-methyl group. N-demethylation was induced after growth in minimal medium, which led to the discovery of the underlying gene MND (morphinan N-demethylase). The MND enzyme has been shown to be robust and versatile, with structurally diverse substrates of N-demethylation at varying temperatures and pH levels. In addition, MND tolerated some organic solvents and maintained its activity once immobilized. These properties make it an attractive candidate for the further development of pharmaceutical manufacturing.