Cryptic Isomerization in Diterpene Biosynthesis and the Restoration of an Evolutionarily Defunct P450

作者：Zining Li, Baofu Xu, Tyler A. Alsup, Xiuting Wei, Wenbo Ning, Daniel G. Icenhour, Michelle Ehrenberger, Ion Ghiviriga, Bao-Doan Giang, Jeffrey D. Rudolf · 发表于：Journal of the American Chemical Society · 年份：2023 · DOI：10.1021/jacs.3c09446 · 被引用次数：19 · 研究领域：Plant biochemistry and biosynthesis、Microbial Natural Products and Biosynthesis、Bioactive Natural Diterpenoids Research

Biosynthetic modifications of the 6/10-bicyclic hydrocarbon skeletons of the eunicellane family of diterpenoids are unknown. We explored the biosynthesis of a bacterial trans -eunicellane natural product, albireticulone A ( 3 ), and identified a novel isomerase that catalyzes cryptic isomerization in the biosynthetic pathway. We also assigned functions of two cytochromes P450 that oxidize the eunicellane skeleton, one of which was a naturally evolved non-functional P450 that, when genetically repaired, catalyzes allylic oxidation. Finally, we described the chemical susceptibility of the trans -eunicellane skeleton to undergo Cope rearrangement to yield inseparable atropisomers.