在Saccharomyces cerevisiae中增强Cannabichromenic酸的生物合成
Mingming Qi1, Tian Liu2, Wenqiang Zhang1
1MOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
ACS synthetic biology
|January 14, 2025
概括
这项研究利用酵母工程从葡萄糖中产生罕见的大麻素CBC (cannabichromene),一种罕见的大麻素. 微生物合成为生产这种促进神经发生的化合物提供了一个可持续的替代方案.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 卡纳比克罗门 (CBC) 是Cannabis sativa L.中含量较低的一种大麻素,具有神经性质.
- 自然的CBC生产受到低效的代谢途径 (DOXP/MEP,脂肪酸代谢) 和CBC合成酶 (CBCAS) 的低活性所限制.
研究的目的:
- 开发一个微生物平台,用于高效的CBCA生物合成.
- 克服前体供应和酶活性的局限性,以提高CBC生产.
主要方法:
- 从葡萄糖和橄酸中合成CBCA生物合成的工程酵母.
- 通过双步异醇利用途径 (IUP) 增强前体供应.
- 通过对内细胞网膜辅助蛋白的共同过度表达和CBCAS的合理设计,改善了CBCA标位.
- 局部化IUP到过氧体以进一步增加geranylgeranyl pyrophosphate和CBCA标位.
主要成果:
- 成功构建了一种能够合成CBCA.的酵母菌株.
- 通过IUP的过氧体局部化实现了geranylgeranyl pyrophosphate的1.6倍增加和CBCA标位的28%增加.
- 与大麻sativa相比,工程酵母表现出比大麻sativa高25.8%的CBCA合成率.
结论:
- 微生物合成为生产CBCA.提供了一个可行的和可持续的替代方案.
- 代谢工程策略有效地增强了有价值的大麻素的生产.
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