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Updated: Oct 25, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Distinct Active-Site Architectures Drive Divergent Catalysis for Convergent Spirooxindole Biosynthesis
Tiandong Hu1,2, Anran Fu2, Qingyu Yang1,2
1State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong266237, China.
Abstract:
Prenylated indole alkaloids containing a spirooxindole scaffold exhibit diverse biological activities. Here, we report that the flavin-dependent monooxygenase PldC catalyzes the conversion of (+)-premalbrancheamide to 3S-hydroxyindolenine, which undergoes spontaneous rearrangement to form 3R-spirooxindole. In contrast, the homologous enzyme PhqK directly furnishes the 3R-spirooxindole from the same substrate. Structural modeling and site-directed mutagenesis reveal that divergent active-site architectures dictate substrate binding orientation, directing epoxide opening to control the product outcome. These findings highlight how distinct active site architectures drive divergent catalysis to achieve convergent spirooxindole biosynthesis.
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