September 22, 2019  |  

A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis.

Authors: Chen, Xue and Hagel, Jillian M and Chang, Limei and Tucker, Joseph E and Shiigi, Stacey A and Yelpaala, Yuora and Chen, Hsiang-Yun and Estrada, Rodrigo and Colbeck, Jeffrey and Enquist-Newman, Maria and Ibáñez, Ana B and Cottarel, Guillaume and Vidanes, Genevieve M and Facchini, Peter J

The ultimate step in the formation of thebaine, a pentacyclic opiate alkaloid readily converted to the narcotic analgesics codeine and morphine in the opium poppy, has long been presumed to be a spontaneous reaction. We have detected and purified a novel enzyme from opium poppy latex that is capable of the efficient formation of thebaine from (7S)-salutaridinol 7-O-acetate at the expense of labile hydroxylated byproducts, which are preferentially produced by spontaneous allylic elimination. Remarkably, thebaine synthase (THS), a member of the pathogenesis-related 10 protein (PR10) superfamily, is encoded within a novel gene cluster in the opium poppy genome that also includes genes encoding the four biosynthetic enzymes immediately upstream. THS is a missing component that is crucial to the development of fermentation-based opiate production and dramatically improves thebaine yield in engineered yeast.

Journal: Nature chemical biology
DOI: 10.1038/s41589-018-0059-7
Year: 2018

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