For nearly eight millennia, opium poppy (Papaver somniferum) has been bred and cultivated for therapeutic purposes. The medicinal properties of the plant are conferred by specialized metabolites known as benzylisoquinoline alkaloids (BIAs), comprising the narcotic analgesics morphine and codeine, the antimicrobial agent sanguinarine, and the potential anticancer drug noscapine. In addition, naturally occurring thebaine is used for the semi-synthesis of widely prescribed pain-relievers (e.g., oxycodone and hydrocodone), valuable drugs used in the treatment of opioid addiction (i.e., naltrexone), or antidotes for opioid overdose (i.e., naloxone). The complex stereochemistry of many opiates hinders their chemical synthesis and opium poppy remains the sole commercial source of these important pharmaceuticals. For decades, opium poppy has served as a model plant for research aimed at a comprehensive understanding of BIA metabolism. Recent progress in functional genomics has enabled the discovery of a nearly complete collection of BIA biosynthetic genes, many of which are clustered in the opium poppy genome. Advances in synthetic biology have facilitated the successful reconstitution of several BIA biosynthetic pathways in heterologous hosts such as Saccharomyces cerevisiae and Escherichia coli, although the initially low production levels suggest that commercial scale-up will present additional challenges. This review provides an update of key molecular and biochemical aspects of BIA metabolism in opium poppy, including recent biosynthetic gene discoveries, genomic organization, novel BIA transporters, metabolic regulation, and major efforts in the engineering of pathways in plants and microbes.

近八千年来，罂粟（罂粟））已为治疗目的而繁殖和培养。这种植物的药用特性是由称为苄基异喹啉生物碱（BIAs）的专门代谢物赋予的，其中包括麻醉性镇痛药吗啡和可待因，抗菌剂血红碱和潜在的抗癌药Noscapine。此外，天然存在的蒂巴因还用于半合成宽处方的止痛药（例如羟考酮和氢可酮），用于治疗阿片类药物成瘾的有价值的药物（即纳曲酮）或用于阿片类药物过量的解毒剂（例如，纳洛酮）。许多鸦片的复杂立体化学阻碍了它们的化学合成，而罂粟仍然是这些重要药物的唯一商业来源。几十年来，鸦片罂粟曾作为研究的样板，旨在全面了解BIA代谢。功能基因组学的最新进展使人们能够发现几乎完整的BIA生物合成基因集合，其中许多聚集在罂粟基因组中。合成生物学的进展促进了在异源宿主中成功重建几种BIA生物合成途径，例如酿酒酵母和大肠杆菌，尽管最初的低产量表明商业规模的生产将面临更多挑战。这篇综述提供了罂粟中BIA代谢的关键分子和生化方面的更新，包括最近的生物合成基因发现，基因组组织，新颖的BIA转运蛋白，代谢调控以及植物和微生物途径工程中的重大努力。