Details

Autor(en) / Beteiligte

• Liu, Zhiwen
• Zhao, Fanglong
• Zhao, Boyang
• Yang, Jie
• Ferrara, Joseph
• Sankaran, Banumathi
• Venkataram Prasad, B. V.
• Kundu, Biki Bapi
• Phillips, George N.
• Gao, Yang
• Hu, Liya
• Zhu, Tong
• Gao, Xue

Titel

Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins

Ist Teil von

• Nature communications, 2021-07, Vol.12 (1), p.1-12, Article 4158

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Prenylated indole alkaloids featuring spirooxindole rings possess a 3 R or 3 S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3 R or 3 S -spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3 S -spirooxindole construction in the biosynthesis of 21 R -citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3 S -spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3 R -spirooxindole, we reveal an evolutionary branch of CtdE in specific 3 S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.