Engineering yeast for high-efficiency isoliquiritigenin production via synthetic biology approaches
10.1097/st9.0000000000000084
- Author:
Yan YIN
1
;
Shucan LIU
2
;
Ting LI
3
;
Ying HUANG
4
;
Xianan ZHANG
5
;
Guangxi REN
6
;
Wei GAO
5
;
Xinghong GUO
2
;
Dan JIANG
6
;
Chunsheng LIU
6
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China; College of Biology, Hunan University, Changsha, China
2. College of Biology, Hunan University, Changsha, China
3. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China; Shaanxi University of Chinese Medicine, Xi’an, China
4. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China; Beijing Newbet Biotech Co., Ltd., Beijing, China
5. School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
6. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- Publication Type:Journal Article
- Keywords:
Glycyrrhiza uralensis;
Isoliquiritigenin;
5-deoxyflavones;
Metabolic engineering;
Saccharomyces cerevisiae
- From:
Science of Traditional Chinese Medicine
2025;3(4):356-365
- CountryChina
- Language:English
-
Abstract:
Background: Isoliquiritigenin, a key pharmacologically active compound derived from the traditional Chinese medicine Glycyrrhizae Radix et Rhizoma, can be further modified into various high-value 5-deoxyflavones, demonstrating significant potential for pharmaceutical development. Currently, the supply of isoliquiritigenin primarily depends on plant extraction. However, heterologous synthesis using microbial cell factories presents a promising alternative, offering a solution to resource limitations caused by the dwindling availability of Glycyrrhiza uralensis. Objective: This study aimed to employ heterologous synthesis in yeast strains for the stable and high-efficiency production of isoliquiritigenin. Methods: First, a stable chassis strain for isoliquiritigenin production was constructed by integrating optimized biosynthetic pathway enzyme genes. A type IV noncatalytic chalcone isomerase-like protein and a synthetic protein scaffold system were employed to enhance the metabolic channeling of key pathway enzymes. Subsequently, yeast metabolism was fine-tuned to balance precursor supply, and cofactor engineering strategies were implemented to increase nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) availability, thereby ensuring the catalytic efficiency of the key enzyme chalcone reductase. Results: The engineered strain Y21-2 achieved a 24.4-fold increase in isoliquiritigenin titer compared to the original strain. Additionally, the proportion of the by-product naringenin chalcone was reduced by 67.8%, marking the first instance in which the ratio of C-5 hydroxylated by-products was minimized to 10.4% during the microbial synthesis of 5-deoxyflavones. Conclusion: This work provides a valuable reference for the efficient and sustainable production of isoliquiritigenin, laying a solid foundation for further pathway optimization and the biotechnological synthesis of other high-value natural 5-deoxyflavones.
