Discovery and engineering the biosynthesis of novel cannabinoid pharmaceuticals

自大麻娱乐和医疗用途合法化以来，加拿大凭借其私营部门和学术界之间的密切联系，一直引领着世界各地的大麻科学和技术发展。随着越来越多的证据表明人类内源性大麻素系统在神经传递和神经保护中的重要性，现在很明显，能够影响其动态平衡的药物将为许多与该系统密切相关的神经退行性疾病和免疫疾病提供新的治疗方法。最近，在几个不相关的植物物种中发现了联苯基大麻类化合物，这是一类新的大麻类化合物，与它们的大麻对应物相比，它们具有更好的新生物活性。它们生物合成的发现和工程将通过提供新的药物来帮助有需要的患者，从而进一步推动大麻类药物的创新。合作伙伴利乐生物制药公司致力于开发含有大麻素衍生分子和其他药用植物成分的生物制药、天然健康和兽医产品。拥有集体的药理学专业知识(利乐生物制药公司)以及天然产物的生物合成(新不伦瑞克大学)，我们将1)揭示联苯基大麻素类化合物的生物合成并进一步设计其结构，2)通过代谢工程开发生物技术以有效地生产它们，以及3)评估它们的生物活性，以便将来将它们开发成临床有用的药物。这个为期3年的项目将允许11名学员参与产学研合作研究，并发展他们的科学和专业技能。该项目的发现和工程努力不仅将有利于未来开发植物性药物的研究，还将为加拿大生物经济和加拿大大麻经济创造价值。

With its strong connections between the private sector and academia, Canada has been leading cannabis science and technology development around the world since the legalization of both recreational and medical uses of cannabis. With mounting evidence of the importance of the human endocannabinoid system in neurotransmission and neuroprotection, it is now clear that pharmaceuticals that can impact its homeostasis will offer new treatments for many neurodegenerative and immune diseases that are closely associated with this system. Recently, bibenzyl cannabinoids, a new class of cannabinoids, have been identified in several unrelated plant species shown to possess superior and new bio activities compared to their cannabis counterparts. Discovery and engineering of their biosynthesis will further cannabinoid innovation by providing new pharmaceuticals to help patients in need. The partner company Tetra Bio Pharma Inc. is engaged in developing biopharmaceuticals, natural health and veterinary products containing cannabinoid-derived molecules and other medicinal plant-based elements. With collective expertise in pharmacology (Tetra Bio Pharma Inc.) and natural product biosynthesis (University of New Brunswick), we will 1) uncover the biosynthesis of bibenzyl cannabinoids and further engineer their structures, 2) develop biotechnology for their efficient production by metabolic engineering, and 3) evaluate their bioactivity for their future development into clinically useful drugs. The 3-year project will allow 11 trainees to participate in industry-academia collaborative research and develop their scientific and professional skills. The discovery and engineering efforts in this project will not only benefit future research on developing plant-based medicines, but also create value to the Canadian bioeconomy and the Canadian cannabis economy.