Engineering a promiscuous prenyltransferase for selective biosynthesis of an undescribed bioactive cannabinoid analog.

ABSTRACT: Cannabinoids are unique meroterpenoids, with cannabigerolic acid (CBGA) serving as a dedicated precursor. This study introduces a fungal aromatic prenyltransferase AscC into the engineered Escherichia coli to catalyze the transfer of C₅-C₁₅ terpenoid linear precursors to olivetolic acid. Four CBGA derivatives (compounds 1-4) with diverse C₅, C₁₀, or C₁₅ prenyl chains are isolated and identified, with compound 4 being an undescribed product featuring a C₁₅ prenyl chain at the C-5 position. Compound 4 demonstrates the highest anti-neuroinflammatory and antibacterial activities, with IC₅₀ values of 3.06 µM for TNF-α and 4.31 µM for IL-6, alongside EC₅₀ values ranging from 0.87 to 3.16 µM against three Gram

SUBMITTER: Yan Q 

PROVIDER: S-EPMC11794439 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature