Engineering yeast peroxisome assembly enables the increased production of acetyl-CoA and its derived 5-deoxyflavonoids.

ABSTRACT: Acetyl-CoA serves as a foundational precursor and energy source for various biosynthesis pathways. The insufficient supply of acetyl-CoA in cytosol is usually a bottleneck for exogenous chemical synthesis in engineered microbes such as yeast. Exportation of acetyl-CoA from peroxisome, an exclusive organelle for fatty acids β-oxidation, may be an effective way to solve this problem. In this study, we develop a peroxin (PEX) engineering strategy to modulate peroxisome assembly in S. cerevisiae. Then, robust peroxisomes are constructed with improved acetyl-CoA supply by up to 98%, which further leads to the increased liquiritigenin titer (1102.4 mg/L). We also demonstrate that the PEX-mediated peroxisome engineering strategy can be extended across yeast species. Hybrid peroxisomes with tailor

SUBMITTER: Li Y 

PROVIDER: S-EPMC12647799 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature