Genomic and cell-specific regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine, and papaverine. Most enzymes involved in benzylisoquinoline alkaloid (BIA) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements, and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition. This review highlights how the biosynthesis of alkaloids in opium poppy is regulated-information that can be used for improving the yield and composition of commercially important compounds.