Ji Dongni, Li Jianhua, Ren Yuhong, Wang Yong
State Key Laboratory of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, China.
CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.
Biotechnol Bioeng. 2022 Jul;119(7):1916-1925. doi: 10.1002/bit.28087. Epub 2022 Apr 6.
Baicalein is a bioactive flavonoid isolated from the traditional Chinese medicinal plant, Scutellaria baicalensis Georgi. Microbial synthesis of flavonoids has been intensively developed owing to the eco-friendly nature of the process. However, the titer of the flavonoids obtained is still at a low level, and effective methods to enhance these titers are lacking. In this study, the synthetic performance of baicalein-producing engineered Escherichia coli was rationally evaluated to enhance the expression of key enzymes. Transcriptional analyses of baicalein-overproducing strain and a control strain enabled the identification of 13 beneficial genes, including eight genes that are seemingly irrelevant to baicalein metabolism. With the combination of the enzyme assembly and modularization strategy, the engineered DN-8 strain produced 367.8 mg/L baicalein in fed-batch fermentation, the maximum titer reported to date.
黄芩素是从传统中药植物黄芩中分离出的一种生物活性黄酮类化合物。由于该过程对环境友好，黄酮类化合物的微生物合成已得到深入发展。然而，所获得的黄酮类化合物的产量仍然很低，并且缺乏提高这些产量的有效方法。在本研究中，对生产黄芩素的工程化大肠杆菌的合成性能进行了合理评估，以增强关键酶的表达。对高产黄芩素菌株和对照菌株的转录分析能够鉴定出13个有益基因，其中包括8个看似与黄芩素代谢无关的基因。通过酶组装和模块化策略的结合，工程化的DN-8菌株在补料分批发酵中产生了367.8mg/L的黄芩素，这是迄今为止报道的最高产量。
