Abstract：
:Ginsenoside Rh2 is a potential anticancer drug isolated from medicinal plant ginseng. Fermentative production of ginsenoside Rh2 in yeast has recently been investigated as an alternative strategy compared to extraction from plants. However, the titer was quite low due to low catalytic capability of the key ginseng glycosyltransferase in microorganisms. Herein, we have demonstrated high-level production of ginsenoside Rh2 in Saccharomyces cerevisiae via repurposing an inherently promiscuous glycosyltransferase, UGT51. The semi-rationally designed UGT51 presented an ~1800-fold enhanced catalytic efficiency (kcat/Km) for converting protopanaxadiol to ginsenoside Rh2 in vitro. Introducing the mutant glycosyltransferase gene into yeast increased Rh2 production from 0.0032 to 0.39mg/g dry cell weight (DCW). Further metabolic engineering, including preventing Rh2 degradation and increasing UDP-glucose precursor supply, increased Rh2 production to 2.90mg/g DCW, which was more than 900-fold higher than the starting strain. Finally, fed-batch fermentation in a 5-L bioreactor led to production of ~300mg/L Rh2, which was the highest titer reported.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Zhuang Y,Yang GY,Chen X,Liu Q,Zhang X,Deng Z,Feng Ydoi
10.1016/j.ymben.2017.04.009subject
Has Abstractpub_date
2017-07-01 00:00:00pages
25-32eissn
1096-7176issn
1096-7184pii
S1096-7176(17)30066-6journal_volume
42pub_type
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