基于合成生物学技术改造酵母高效合成萜类化合物  

Synthetic biology for terpenoids producing efficiently in yeasts

作　　者：尹梦琦 赵建志 YIN Mengqi;ZHAO Jianzhi(State Key Laboratory of Biobased Material and Green Papermaking,School of Bioengineering,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250353,China)

机构地区：[1]齐鲁工业大学(山东省科学院)生物工程学院生物基材料与绿色造纸国家重点实验室,山东济南250353

出　　处：《齐鲁工业大学学报》2025年第1期36-46,共11页Journal of Qilu University of Technology

基　　金：国家重点研发计划(2018YFB1501401);山东省自然科学基金(ZR2020MC016);齐鲁工业大学(山东省科学院)科教产重大创新专项(2022JBZ01-06);山东省技术创新引导计划项目(02055183)。

摘　　要：萜类化合物是一类以异戊烯基二磷酸(isopentenyl diphosphate,IPP)和二甲基烯丙基二磷酸(dimethylallyl diphosphate,DMAPP)为基本前体经相应萜类合成酶催化形成的天然产物,几乎存在于所有生物体中,以药用植物居多,并在医药、食品、化工及能源等领域有着广泛应用。萜类化合物通常采用植物提取法和化学合成法获得,但这两种方法存在效率低、质量不稳定、成本高等弊端,这显然已不能满足对萜类化合物日益增长的需求。随着合成生物学技术的快速发展,改造微生物合成萜类化合物取得了巨大进步,特别是酵母细胞,因其具有与植物细胞类似的结构及较为成熟的遗传操作体系,已用于多种萜类化合物的合成,逐渐凸显出生物合成法的优势。以酿酒酵母(Saccharomyces cerevisiae)和解脂耶氏酵母(Yarrowia lipolytica)两种模式酵母为例,综述重要萜类化合物高效合成的代谢工程改造研究进展,具体从高活性萜类合成酶的筛选与表达、关键前体乙酰辅酶A的供给与高效利用、直接前体单元IPP和DMAPP合成通量强化与消耗弱化等方面改造策略进行了详细介绍,最后,还对酵母合成萜类化合物研究将来面对的机遇与挑战进行了总结与展望。Terpenoids,natural products formed from isopentenyl diphosphate(IPP)and dimethylallyl diphosphate(DMAPP)as precursors,are almost ubiquitous in all organisms,with medicinal plants being predominant.They find wide applications in pharmaceuticals,food,chemical,and energy industries.The extraction from plants and chemical synthesis are commonly employed methods to obtain terpenoids.However,both methods suffer from drawbacks such as low efficiency,unstable quality,and high costs.These limitations clearly cannot meet the increasing demand for terpenoids.With the rapid development of synthetic biology techniques,significant progress has been made in engineering microorganisms for the synthesis of terpenoids,particularly yeast cells.Yeast cells,owing to their similar structure to plant cells and mature genetic manipulation systems,have been utilized for the synthesis of various terpenoids,gradually showcasing the advantages of biosynthetic approaches.This article reviews the progress of metabolic engineering for efficient synthesis of important terpenoids using two model yeasts,Saccharomyces cerevisiae and Yarrowia lipolytica,as examples.Specifically,it summarizes various strategies for metabolic engineering,including the screening and expression of highly active terpenoid synthases,the supply and efficient utilization of key precursor acetyl-CoA,as well as strategies for enhancing the synthesis flux of direct precursors,IPP and DMAPP,while minimizing their consumption.Finally,the article concludes with a summary and outlook on the opportunities and challenges faced by yeast-based synthesis of terpenoids.

关 键 词：酿酒酵母 解脂耶氏酵母 合成生物学技术 代谢途径优化 萜类化合物 

分 类 号：Q936[生物学—微生物学]