Cryptic Isomerization in Diterpene Biosynthesis and the Restoration of an Evolutionarily Defunct P450.
Cryptic Isomerization in Diterpene Biosynthesis and the Restoration of an Evolutionarily Defunct P450.
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二萜生物合成中的隐秘异构化和进化失效的 P450 的恢复。
DOI：
10.1021/jacs.3c09446
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发表时间：
2023
影响因子：
15
通讯作者：
Rudolf,JeffreyD
中科院分区：
文献类型：
--
作者：
Li,Zining;Xu,Baofu;Alsup,TylerA;Wei,Xiuting;Ning,Wenbo;Icenhour,DanielG;Ehrenberger,MichelleA;Ghiviriga,Ion;Giang,Bao-Doan;Rudolf,JeffreyD
二萜类单胞菌烷家族的 6/10-双环烃骨架的生物合成修饰尚不清楚。我们探索了细菌反单胞菌天然产物 albireticulone A (3) 的生物合成，并鉴定了一种新型异构酶，可催化生物合成途径中的隐性异构化。我们还指定了两种氧化单胞菌骨架的细胞色素 P450 的功能，其中一种是自然进化的非功能性 P450，当经过基因修复后，可催化烯丙基氧化。最后，我们描述了反式单胞烷骨架进行 Cope 重排以产生不可分离的阻转异构体的化学敏感性。
Biosynthetic modifications of the 6/10-bicyclic hydrocarbon skeletons of the eunicellane family of diterpenoids are unknown. We explored the biosynthesis of a bacterialtrans-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 thetrans-eunicellane skeleton to undergo Cope rearrangement to yield inseparable atropisomers.