Systematic Metabolic Engineering for the Production of Azaphilones in Monascus purpureus HJ11
Systematic Metabolic Engineering for the Production of Azaphilones in Monascus purpureus HJ11
复制标题
紫红曲霉 HJ11 生产阿扎菲酮类化合物的系统代谢工程
DOI：
10.1021/acs.jafc.1c07588
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发表时间：
2022-02-09
影响因子：
6.1
通讯作者：
Li, Mu
中科院分区：
文献类型：
--
作者：
Duan, Yali;Du, Yun;Li, Mu
真菌氮杂环酮类化合物在食品和医药工业中显示出巨大的潜力，因此引起了人们的极大兴趣。然而，在野生菌株产量低和基因工程产生氮杂环丙酮真菌的能力方面存在严重的瓶颈。以红曲霉氮杂环己酮(MAS)为例，我们展示了一种提高MAS产量的系统代谢工程策略。在本研究中，通过启动子工程、基因敲除、限速酶的过度表达、竞争途径的抑制、酶工程和代谢再平衡的组合，对红曲霉HJ11进行了系统的工程。MAS的最高产量和效价分别提高到906 mg/g干细胞重和14.6g/L，分别是文献报道的2.6倍和3.7倍。我们的成功模型不仅为提高氮杂环丙酮的产量提供了一种实用而有效的方法，而且还揭示了非模式真菌作为生产高价值化学品的底盘的系统代谢工程的潜力。
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.