Systematic optimization of the yeast cell factory for sustainable and high efficiency production of bioactive ginsenoside compound K  

作　　者：Pingping Wang Jiali Wang Guoping Zhao Xing Yan Zhihua Zhou 

机构地区：[1]CAS-Key Laboratory of Synthetic Biology,CAS Center for Excellence in Molecular Plant Sciences,Institute of Plant Physiology and Ecology,Chinese Academy of Sciences,300 Fenglin Rd,Shanghai,200032,China [2]School of Life Sciences,Henan University,Kaifeng,475001,China

出　　处：《Synthetic and Systems Biotechnology》2021年第2期69-76,共8页合成和系统生物技术（英文）

基　　金：supported by the National Key Research and Development Program of China(Grant No.2018YFA0900700);the Drug Innovation Major Project(2018ZX09711001-006-002);the National Natural Science Foundation of China(Nos.31901021,31921006,and 32071425);the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB27020206);the Strategic Biological Resources Service Network Plan of the Chinese Academy of Sciences(Grant No.KFJ-BRP-009);the National Key Research and Development Program of Yunnan Province(2019ZF011-1).

摘　　要：Ginsenoside Compound K(CK)has been recognized as a major functional component that is absorbed into the systemic circulation after oral administration of ginseng.CK demonstrates diverse bioactivities.A phase I clinical study indicated that CK was a potential candidate for arthritis therapy.However,a phase II clinical study was suspended because of the high cost associated with the present CK manufacturing approach,which is based on the traditional planting-extracting-biotransforming process.We previously elucidated the complete CK biosynthetic pathway and realized for the first time de novo biosynthesis of CK from glucose by engineered yeast.However,CK production was not sufficient for industrial application.Here,we systematically engineered Saccharomyces cerevisiae to achieve high titer production of CK from glucose using a previously constructed protopanaxadiol(PPD)-producing chassis,optimizing UGTPg1 expression,improving UDP-glucose biosynthesis,and tuning down UDP-glucose consumption.Our final engineered yeast strain produced CK with a titer of 5.74 g/L in fed-batch fermentation,which represents the highest CK production in microbes reported to date.Once scaled-up,this high titer de novo microbial biosynthesis platform will enable a robust and stable supply of CK,thus facilitating study and medical application of CK.

关 键 词：Compound K UDP-GLUCOSE Glycosylation efficiency Cell factory Synthetic biology 

分 类 号：Q2[生物学—细胞生物学]