Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation

• DOI: 10.1038/s41467-022-34313-6
• Publication Date: 2022-11-09T12:02:56Z
• Authors: Natali Ozber; Samuel C. Carr; Jeremy S. Morris; Siyu Liang; Jacinta L. Watkins; Kristian M. Caldo; Jillian M. Hagel; Kenneth K. S. Ng; Peter J. Facchini
• Keywords: Benzylisoquinoline; Opium Poppy; Sanguinarine; Papaveraceae

Abstract Opium poppy accumulates copious amounts of several benzylisoquinoline alkaloids including morphine, noscapine, and papaverine, in the specialized cytoplasm laticifers, which compose an internal secretory system associated with phloem throughout plant. The contiguous latex includes abundance related proteins belonging to pathogenesis-related (PR)10 family known collectively as major (MLPs) representing at least 35% total cellular protein content. Two MLP/PR10 proteins, thebaine synthase neopione isomerase, have recently been shown catalyze late steps morphine biosynthesis previously assigned spontaneous reactions. Using a combination sucrose density-gradient fractionation-coupled proteomics, differential scanning fluorimetry, isothermal titration calorimetry, X-ray crystallography, we show that are alkaloid-binding display altered conformation presence certain ligands. Addition yeast strains engineered biosynthetic genes from plant significantly enhanced conversion salutaridine morphinan alkaloids.