构建酿酒酵母工程菌合成香紫苏醇

Engineering Saccharomyces cerevisiae for sclareol production

摘要:

香紫苏醇是一种来源于植物的双环二萜醇，常用于香味成分且具有重要生物学活性。为实现香紫苏醇的微生物生产，以酿酒酵母为宿主，表达焦磷酸赖百当烯二醇酯合酶和香紫苏醇合酶，构建香紫苏醇的人工生物合成途径。发现过表达前体代谢关键酶、蛋白质融合增强底物通道效应及去除异源蛋白信号肽等，有利于香紫苏醇合成。在摇瓶培养条件下，组合优化得到的工程菌株S6的香紫苏醇产量达到8.96 mg/L。研究结果对其他萜类化合物的异源生物合成具有参考价值。

关键词:香紫苏醇，酿酒酵母，二萜化合物，生物合成，合成生物学

Abstract:

Sclareol is a member of labdane type diterpenes mostly used as fragrance ingredient. To enable microbial production of sclareol, synthetic pathways were constructed by incorporating labdenediol diphosphate synthase (LPPS) and terpene synthase (TPS) of the plant Salvia sclarea into Saccharomyces cerevisiae. It was found that sclareol production could be benefited by overexpression of key enzyme for precursor biosynthesis, construction of fusion protein for substrate channeling, and removal of signal peptides from LPPS and TPS. Under optimal shake flask culture conditions, strain S6 produced 8.96 mg/L sclareol. These results provided useful information for development of heterologous hosts for production of terpenoids.

Key words:sclareol, Saccharomyces cerevisiae, diterpenoids, biosynthesis, synthetic biology