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Greening production of opiate-addiction treatments

Enzyme morphinan N-demethylase for more sustainable opiate processing

Along with codeine and morphine, the opium poppy, pictured, produces thebaine, which can be used to create opiate-addiction treatments. However, it must first be processed using toxic reactants that produce harmful waste. Kutchan et al. probed an opium-processing waste stream and identified a versatile enzyme that can be used instead.

By Kutchan et al.

Naturally occurring opiates, such as morphine and thebaine, are produced in poppy species. Thebaine is converted into painkillers and opiate addiction treatments, the latter requiring a chemical reaction called N-demethylation. Current opiate N-demethylation utilizes noxious reagents, resulting in copious amounts of harmful waste. One way to make opiate production more sustainable is to use enzymes rather than chemicals. Microorganisms provide a rich source of enzymes useful for metabolizing unique compounds in their environment. Therefore, an opium-processing waste stream was probed to identify an organism capable of catalysing opiate N-demethylation. A sludge sample was grown on minimal medium containing thebaine as the sole carbon source, to identify a biocatalyst. This led to the discovery of Thebainfresser, a Methylobacterium that metabolizes opiates by removing the N-methyl group. N-demethylation was induced following growth in minimal medium, a characteristic which led to discovery of the underlying gene MND (morphinan N-demethylase). The enzyme MND was found to be robust and versatile, N-demethylating structurally diverse substrates at varying temperatures and pH levels. In addition, MND tolerated selected organic solvents and maintained activity when immobilized. These properties make it an attractive candidate for further development for pharmaceutical manufacture.

Nature Sustainability volume 2, pages465–474 (2019)


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