Biosynthesis of the Immunosuppressant (−)-FR901483
Zhuan Zhang, Yui Tamura, Man‐Cheng Tang, Tianzhang Qiao, Michio Sato, Yoshihiro Otsu, Satoshi Sasamura, Masatoshi Taniguchi, Kenji Watanabe, Yi Tang
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.
Topics & Concepts
ChemistryAldol condensationStereoselectivityBiosynthesisRegioselectivityStereochemistryPiperazineAnnulationHeterologousIndole alkaloidHeterologous expressionAlkaloidCombinatorial chemistryEnzymeBiochemistryRecombinant DNAOrganic chemistryCatalysisGeneMarine Sponges and Natural ProductsBioactive Compounds and Antitumor AgentsMicrobial Natural Products and Biosynthesis