Biosynthesis of the Immunosuppressant (-)-FR901483.
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ABSTRACT: We report characterization of the biosynthetic pathway of the potent immunosuppressant (-)-FR901483 (1) through heterologous expression and enzymatic assays. The biosynthetic logic to form the azatricyclic alkaloid is consistent with those proposed in biomimetic syntheses and involves aza-spiro annulation of dityrosyl-piperazine to form a ketoaldehyde intermediate, followed by regioselective aldol condensation, stereoselective ketoreduction, and phosphorylation. A possible target of 1 is proposed based on the biosynthetic studies.
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8094545 | biostudies-literature |
REPOSITORIES: biostudies-literature
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