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Updated: May 14, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Deciphering Early Oxidative Steps in Spirotetronate Biosynthesis Reveals a Two-Enzyme Cascade for Macrocyclic Lactone
Siqiang Chen1,2, Zuer Lin1,2, Qingbo Zhang1,2
1State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Abstract:
We decipher functions of three monooxygenases (PasO1, PasO3, and PasO4) in early biosynthetic steps in spirotetronate PA-46101 and demonstrate a PasO4/PasO3 cascade for forging the signature macrocyclic lactone. The P450 PasO4 oxidizes a methyl group to a carboxylate, enabling a regiospecific Baeyer-Villiger oxidation by PasO3. Structural analysis of a PasO3 homologue identifies a carboxylate-binding pocket essential for this strict substrate specificity. This two-enzyme cascade can serve as a portable biocatalytic tool for diversifying spirotetronates.
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