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Biosynthesis of the Immunosuppressant (-)-FR901483.

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 | 2021 Jan

REPOSITORIES: biostudies-literature

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Biosynthesis of the Immunosuppressant (-)-FR901483.

Zhang Zhuan Z Tamura Yui Y Tang Mancheng M Qiao Tianzhang T Sato Michio M Otsu Yoshihiro Y Sasamura Satoshi S Taniguchi Masatoshi M Watanabe Kenji K Tang Yi Y

Journal of the American Chemical Society 20201229 1

We report characterization of the biosynthetic pathway of the potent immunosuppressant (-)-FR901483 (<b>1</b>) 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 <b>1< ...[more]

PMID: 33372776

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