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Systematic Metabolic Engineering for the Production of Azaphilones in Monascus purpureus HJ11
Yali Duan1, Yun Du1, Zhiqiang Yi1
1College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei Province, China.
Abstract:
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.
Insights
Metabolic engineering significantly boosted fungal azaphilone production. This study presents a systematic strategy to enhance Monascus azaphilones (MAs) yield and titer in Monascus purpureus, offering a new pathway for high-value chemical production.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Fungal Biotechnology
Background:
- Fungal azaphilones show promise in food and pharmaceuticals.
- Low production yields and genetic manipulation challenges hinder their industrial application.
Purpose of the Study:
- To develop and demonstrate a systematic metabolic engineering strategy for enhancing Monascus azaphilone (MA) production in *Monascus purpureus*.
- To overcome the limitations of low yields and genetic tractability in azaphilone-producing fungi.
Main Methods:
- Systematic metabolic engineering of *Monascus purpureus* HJ11.
- Utilized promoter engineering, gene knockout, enzyme overexpression, pathway repression, enzyme engineering, and metabolic rebalancing.
Main Results:
- Achieved a maximum MA yield of 906 mg/g dry cell weight (DCW).
- Reached a maximum MA titer of 14.6 g/L, representing a 2.6-fold increase in yield and a 3.7-fold increase in titer compared to literature values.
Conclusions:
- The developed metabolic engineering strategy provides an efficient method for improving azaphilone production.
- This model highlights the potential of systematic metabolic engineering in nonmodel fungi for producing high-value chemicals.
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