酵母中的大麻素及其非自然类型的完整生物合成
Xiaozhou Luo1, Michael A Reiter1,2, Leo d'Espaux3,4
1California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA.
Nature
|March 1, 2019
概括
科学家从糖中改造酵母来产生主要的大麻素, 包括四大麻酸和大麻酸. 这一突破使大麻化合物可用于医学研究和药物开发.
科学领域:
- 生物技术
- 合成生物学
- 医学化学
背景情况:
- 大麻sativa L. 具有长期的药用历史,大麻素具有治疗潜力.
- 大麻素研究的挑战包括法律限制,低自然丰富性和复杂的合成.
- 有批准的大麻素药物存在, 但需要更广泛的化合物进行进一步研究.
研究的目的:
- 开发一种可持续且可扩展的生产大麻素及其类型的方法.
- 克服传统大麻素提取和化学合成的局限性.
- 创建一个平台发现新的大麻基疗法.
主要方法:
- 从银河糖生物合成大麻素的工程细菌.
- 优化了对高酸流量的美酸路径.
- 引入异构的六CoA通路和大麻衍生基因用于大麻素生物合成.
- 利用基因杂交和脂肪酸养来产生大麻素类似物.
- 综合生物生产与合成化学扩大化学多样性.
主要成果:
- 实现主要大麻素的完整生物合成:大麻素酸,Δ9-四大麻素酸,大麻素酸,Δ9-四大麻素酸和大麻素酸.
- 通过修改脂肪酸前体成功制造了大麻素类似物.
- 通过生物合成和合成方法创建新型大麻素结构的潜力.
结论:
- 开发了一个以酵母为基础的平台,
- 这种系统有助于研究天然和非天然的大麻素的潜在医学应用.
- 该平台为大麻素领域的药物发现和开发提供了可扩展的解决方案.
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