大黄素
发酵
去甲基化
生物
生物化学
生物转化
生物生产
化学
基因表达
酶
DNA甲基化
基因
作者
Feifei Qi,Wei Zhang,Yingying Xue,Ce Geng,Jin Zhigang,Jibin Li,Qiang Guo,Xiaowan Huang,Xuefeng Lü
标识
DOI:10.1016/j.ymben.2022.10.007
摘要
Physcion is a characteristic component of the traditional herb rhubarb with diverse pharmacological activities that has been commercially approved as an herbal fungicide. Nevertheless, its extremely low contents, costly purification procedure and geographically restricted planting severely hinder its application. Here, a cell factory was constructed in the filamentous fungus Aspergillus terreus for physcion production via microbial fermentation by integrating a pathway-modified emodin accumulation module and a position-selective emodin methylation module. Specifically, 1.71 g/L emodin accumulated when the transcriptional activator GedR and the emodin-1-OH-O-methyltransferase GedA in the geodin biosynthetic pathway were overexpressed and knocked out, respectively. Subsequently, potential emodin-3-OH-O-methyltransferase candidates were enzymatically screened in vitro and introduced into the emodin-accumulating mutant in vivo to generate a physcion-producing strain showing the highest titre of 6.3 g/L in fed-batch fermentation. Thus, our study provides an alternative strategy for the highly efficient, economical production of physcion and a representative example for microbial synthetic biology.
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