Chemically guided single-cell transcriptomics reveals sulfotransferase-mediated scaffold remodeling in securinine biosynthesis.

ABSTRACT: Securinega alkaloids possess a distinctive tetracyclic scaffold and are pharmaceutically relevant, yet their biosynthesis in Flueggea suffruticosa remains unresolved. Here, we combine chemical logic with stable-isotope-labeled feeding experiments and single-cell transcriptomics to elucidate the core biosynthetic pathway. We identify a reductase, FsMS, that reduces premenisdaurilide to menisdaurilide, which then conjugates with 1-piperideine to generate the [2.2.2]-bicyclic neosecurinanes, (-)-virosine A and (-)-virosine B. We also identify two sulfotransferases, FsNSST1 and FsNSST2, that O-sulfate these neosecurinanes; the resulting sulfate esters undergo a spontaneous 1,2-amine shift to yield the [3.2.1]-bicyclic securinanes, allosecurinine and securinine. This transformation reveals an u

SUBMITTER: Choung S 

PROVIDER: S-EPMC12929733 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature