Cannabis sativa is a source of food, fiber and specialized metabolites such as cannabinoids, with psychoactive and pharmacological effects. Due to its expanding and increasingly-accepted use in medicine, cannabis cultivation is acquiring more importance and less social stigma. Humans initiated different domestication episodes whose later spread gave rise to a plethora of landrace cultivars. At present, breeders cross germplasms from different gene pools depending on their specific use. The fiber (hemp) and drug (marijuana) types of C. sativa differ in their cannabinoid chemical composition phenotype (chemotype) and also in the accumulation of terpenoid compounds that constitute a strain's particular flavor and scent. Cannabinoids are isoprenylated polyketides among which cannabidiolic acid (CBDA) and (-)-trans-Δ⁹-tetrahydrocannabinol acid (THCA) have been well-documented for their many effects on humans. Here, we review the most studied specialized metabolic pathways in C. sativa, showing how terpenes and cannabinoids share both part of the isoprenoid pathway and the same biosynthetic compartmentalization (i.e. glandular trichomes of leaves and flowers). We enlist the several studies that have deciphered these pathways in this species including physical and genetic maps, QTL analyses and localization and enzymatic studies of cannabinoid and terpene synthases. In addition, new comparative modeling of cannabinoid synthases and phylogenetic trees are presented. We describe the genome sequencing initiatives of several accessions with the concomitant generation of next-generation genome maps and transcriptomic data. Very recently, proteomic characterizations and systems biology approaches such as those applying network theory or the integration of multi-omics data have increased the knowledge on gene function, enzyme diversity and metabolite content in C. sativa. In this revision we drift through the history, present and future of cannabis research and on how second- and third-generation sequencing technologies are bringing light to the field of cannabis specialized metabolism. We also discuss different biotechnological approaches for producing cannabinoids in engineered microorganisms.

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系统生物学时代对大麻特化代谢的理解与提升

大麻是食物、纤维和特殊代谢物（如大麻素）的来源，具有精神和药理作用。由于其在医学中的应用不断扩大和越来越被接受，大麻种植变得越来越重要，社会耻辱感越来越少。人类发起了不同的驯化事件，后来的传播产生了大量的地方品种。目前，育种者根据其特定用途从不同基因库中杂交种质。C. sativa 的纤维（大麻）和药物（大麻）类型的区别在于它们的大麻素化学成分表型（化学型）以及构成菌株特定风味和气味的萜类化合物的积累。大麻素是异戊二烯化聚酮化合物，其中大麻二酚酸 (CBDA) 和 (-)-反式-Δ⁹-四氢大麻酚酸 (THCA) 已被充分证明对人类的许多影响。在这里，我们回顾了 C. sativa 中研究最多的专门代谢途径，展示了萜烯和大麻素如何共享类异戊二烯途径的一部分和相同的生物合成区室化（即叶和花的腺毛）。我们征集了几项已破译该物种中这些途径的研究，包括物理和遗传图谱、QTL 分析以及大麻素和萜烯合酶的定位和酶学研究。此外，还介绍了大麻素合酶和系统发育树的新比较模型。我们描述了几个种质的基因组测序计划，同时生成了下一代基因组图谱和转录组数据。最近，蛋白质组学表征和系统生物学方法，例如应用网络理论或多组学数据整合的方法，增加了对 C. sativa 中基因功能、酶多样性和代谢物含量的了解。在本次修订中，我们详细介绍了大麻研究的历史、现在和未来，以及第二代和第三代测序技术如何为大麻专门代谢领域带来光明。我们还讨论了在工程微生物中生产大麻素的不同生物技术方法。蛋白质组学表征和系统生物学方法，例如应用网络理论或多组学数据整合的方法，增加了对 C. sativa 中基因功能、酶多样性和代谢物含量的了解。在本次修订中，我们详细介绍了大麻研究的历史、现在和未来，以及第二代和第三代测序技术如何为大麻专门代谢领域带来光明。我们还讨论了在工程微生物中生产大麻素的不同生物技术方法。蛋白质组学表征和系统生物学方法，例如应用网络理论或多组学数据整合的方法，增加了对 C. sativa 中基因功能、酶多样性和代谢物含量的了解。在本次修订中，我们详细介绍了大麻研究的历史、现在和未来，以及第二代和第三代测序技术如何为大麻专门代谢领域带来光明。我们还讨论了在工程微生物中生产大麻素的不同生物技术方法。大麻研究的现状和未来，以及第二代和第三代测序技术如何为大麻专门代谢领域带来光明。我们还讨论了在工程微生物中生产大麻素的不同生物技术方法。大麻研究的现状和未来，以及第二代和第三代测序技术如何为大麻专门代谢领域带来光明。我们还讨论了在工程微生物中生产大麻素的不同生物技术方法。