Engineering Sanghuangporus sanghuang for enhanced (-)-aristolone production via metabolic pathway optimization and terpene synthase engineering.

ABSTRACT: (-)-Aristolone, a sesquiterpene with promising therapeutic properties such as antidiabetic and vasorelaxant effects, currently suffers from limited availability due to inefficient chemical synthesis and lack of viable extraction methods. This study presents a novel strategy for high-yield microbial (-)-aristolone production using Sanghuangporus sanghuang DM989 as a fungal chassis. Genome mining identified nine sesquiterpene synthases, among which TPS2152 was functionally linked to (-)-aristolone biosynthesis. TPS2152 harbors a rare DQxxD motif, diverging from the canonical DDxxD motif in plants, suggesting unique catalytic properties in fungi. Overexpression of farnesyl pyrophosphate synthase (FPPS) increased FPP precursor supply, resulting in a 78.79% rise in squalene content (1.18 mg/g)

SUBMITTER: Li Y 

PROVIDER: S-EPMC12209383 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature