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Rational design of DAHP synthase and prephenate dehydrogenase for metabolic engineering of Bacillus amyloliquefaciens to produce L-tyrosine

合理设计DAHP合成酶和预苯酸脱氢酶以实现枯草芽孢杆菌的代谢工程改造用于生产L-酪氨酸

关键词:
来源:
International Journal of Biological Macromolecules
来源地址:
https://doi.org/10.1016/j.ijbiomac.2025.142076
类型:
学术文献
语种:
英语
原文发布日期:
2025-03-14
摘要:
The rational design of enzymes represents a critical strategy for achieving efficient and sustainable biocatalysis. In this study, enzyme evolution guided by rational design was utilized to engineer two key enzymes, DAHP synthase (AroA) and prephenate dehydrogenase (TyrA), within the biosynthetic pathway of L-tyrosine. The beneficial mutants AroAR27A/K38A and TyrAI309A/E330V were identified, leading to a 102 % and 105 % increase in L-tyrosine yield, respectively. Molecular dynamics simulations further explained the possible mechanism underlying their improved catalytic efficiency. Co-expression of these two mutant genes resulted in a significant increase in L-tyrosine yield. Additionally, modifications in the branching metabolic pathways, which altered both material and energy flux, further enhanced L-tyrosine production. Ultimately, the L-tyrosine yield (0.14 g/g) from xylose was much higher than that from glucose, and the final L-tyrosine titer (9.39 g/L) and productivity (0.26 g/(L·h)) were achieved through fermentation optimization in shake flasks. This represents the highest reported yield in shake flasks. The strategies described here will contribute to the development of microbial strains for the efficient production of L-tyrosine from sustainable biomass resources.
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