High-level biosynthesis of gastrodin in engineered Escherichia coli
Lin Ge1, Ruobing Jia2, Wenxin Xu3
1College of Biopharmacy, Suzhou Chien-Shiung Institute of Technology, 1 Jian Xiong Road, Taicang 215411, China; Jiangsu Provincial Novel Anti-tumor Targeted Drug Conjugate Engineering Research Center, Suzhou 215411, China.
None:
Gastrodin is the principal bioactive component of Gastrodia elata, which is famous for its many remarkable pharmacological properties. In this study, several UDP-glycosyltransferases from different sources were used to evaluate and compare the biotransformation ability of p-hydroxybenzyl alcohol to gastrodin. The recombinant strain BL-RrUGT, expressing the UDP-glycosyltransferase (RrUGT) from Rhodiola rosea, exhibited the highest initial titer of 210.60 mg/L. To further augment production, we enhanced the intracellular UDP-glucose level in Escherichia coli (E. coli) K12 by overexpressing two pivotal biosynthetic enzymes: phosphoglucomutase and UDP-glucose pyrophosphorylase. This metabolic engineering strategy yielded the recombinant strain BL-Rr-PG, which boosted the gastrodin titer to 342.40 mg/L. Subsequently, the culture medium and fermentation conditions were optimized. This resulted in a maximum gastrodin titer of 4578.03 mg/L, with a specific productivity of 69.36 mg/L/h and a molar conversion rate of 82.72%. This output represents the highest yield of gastrodin reported in E. coli to date.
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