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开发一个高效的酵母平台,用于可纳比基洛酸生物合成

Yunfeng Zhang¹, Jiulong Guo², PeiZhen Gao²

¹Shenzhen Key Laboratory for the Intelligent Microbial Manufacturing of Medicines, CAS Key Laboratory of Quantitative Engineering Biology, Center for Synthetic Biochemistry, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Metabolic engineering

|October 27, 2023

概括

研究人员对Saccharomyces cerevisiae进行了改造,以产生高位的治疗性大麻素CBGA,一种治疗性大麻素. 这一突破显著提高了CBGA的生产,用于潜在的制药应用.

科学领域:

生物技术是生物技术.
代谢工程是代谢工程.
合成生物学合成生物学

背景情况:

类大麻素,如 cannabigerolic 酸 (CBGA),对各种人类疾病,包括癌症和 SARS-CoV-2 感染,具有显著的治疗潜力.
大麻sativa前基转移酶 (CsPT4) 合成CBGA,但由于代谢瓶和酶限制,Saccharomyces cerevisiae中的微生物生产产生了低于最佳的标位.

研究的目的:

为了改造Saccharomyces cerevisiae以提高可纳米基洛酸 (CBGA) 的生产.
为了克服六酸盐转化中的局限性,并改善大麻树种前基转移酶 (CsPT4) 酶的活性和稳定性.

主要方法:

使用代谢工程策略,通过β-氧化途径减少六酸盐的消耗,并最大限度地减少其纳入脂肪酸.
细胞工程涉及扩大内质网膜,并将辅助蛋白与CsPT4融合以提高其性能.
工程酵母底盘是使用葡萄糖和六酸盐作为基质进行培养的.

主要成果:

改造的Saccharomyces cerevisiae在CBGA产量上显著增加了78.64倍.
最终的CBGA标位达到了510.32±10.70毫克L-1.1.
结合的代谢和蛋白质工程策略有效地解决了微生物CBGA合成的挑战.

结论:

开发的工程酵母菌株代表了微生物CBGA生产的重大进步.
这种增强的生产平台对治疗性大麻素的经济高效和可扩展的合成具有前景.
进一步优化可能会导致制药应用的产量更高.

关键词:

这是一种大麻素 (cannabinoid).脂肪酸合成脂肪酸合成甲基转移作为一个转移这种植物是Saccharomyces cerevisiae.类化物类化物

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