紫色红曲霉
红曲霉
代谢工程
生物
生物技术
底盘
合成生物学
生产(经济)
酶
食品科学
计算生物学
生物化学
发酵
工程类
经济
宏观经济学
结构工程
作者
Yali Duan,Yun Du,Zhiqiang Yi,Zhe Wang,Xiaolin Pei,Xuetuan Wei,Mu Li
标识
DOI:10.1021/acs.jafc.1c07588
摘要
Fungal azaphilones have attracted considerable interest as they exhibit great potential in food and pharmacological industries. However, there is a severe bottleneck in the low production in wild strains and the ability to genetically engineer azaphilone-producing fungi. Using Monascus azaphilones (MAs) as an example, we demonstrate a systematic metabolic engineering strategy for improving the production of MAs. In this study, Monascus purpureus HJ11 was systematically engineered through a combination of promoter engineering, gene knockout, rate-limiting enzyme overexpression, repression of the competing pathway, enzyme engineering, and metabolic rebalance. The maximum yield and titer of MAs successfully increased to 906 mg/g dry cell weight (DCW) and 14.6 g/L, respectively, 2.6 and 3.7 times higher than those reported in the literature. Our successful model not only offers a practical and efficient way to improve the azaphilone production but also sheds light on the potential of systematic metabolic engineering in nonmodel fungi as a chassis for the production of high-value chemicals.
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