Abstract：
Cannabidiol (CBD), the main nonpsychoactive cannabinoid in Cannabis sativa, has diverse applications in the pharmacological, food, and cosmetic industries. The long plantation period and the complex chemical structure of cannabidiol pose a great challenge on CBD supply. Here, we achieved de novo biosynthesis of cannabidiol in Saccharomyces cerevisiae. The CBD production was further enhanced by 2.53-fold through pushing the supply of precursors and fusion protein construction. Bile pigment transporter 1 (BPT1) was the most effective transporter for transferring cannabigerolic acid (CBGA) from the cytoplasm to the vacuole, which removed the physical barrier separating CBGA and its catalytic enzyme. The lowest binding energy of the CBGA-BPT1 complex confirmed a strong interaction between BPT1 and CBGA. A CBD yield of 6.92 mg/L was achieved, which was 100-fold higher than the yield generated by the starting strain. This study provides insights into high-level CBD-producing strain construction and lays the foundation for CBD supply.
摘要：
大麻二酚（CBD），大麻中主要的非精神活性大麻素，在药理学中有不同的应用，食物,和化妆品行业。大麻二酚的长期种植和复杂的化学结构对CBD的供应构成了巨大的挑战。这里,我们在酿酒酵母中实现了大麻二酚的从头生物合成。通过推动前体的供应和融合蛋白的构建，CBD的产量进一步提高了2.53倍。胆汁色素转运蛋白1（BPT1）是将大麻酚酸（CBGA）从细胞质转移到液泡的最有效的转运蛋白，去除分离CBGA及其催化酶的物理屏障。CBGA-BPT1复合物的最低结合能证实了BPT1和CBGA之间的强相互作用。CBD产量为6.92mg/L，比起始菌株产生的产量高100倍。本研究为构建高水平CBD生产菌株提供了见解，并为CBD供应奠定了基础。
