Structure of the Dioxygenase AsqJ: Mechanistic Insights into a OnePot Multistep Quinolone Antibiotic Biosynthesis
Structure of the Dioxygenase AsqJ: Mechanistic Insights into a OnePot Multistep Quinolone Antibiotic Biosynthesis
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DOI：
10.1002/anie.201507835
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发表时间：
2016-01-04
影响因子：
16.6
通讯作者：
Groll, Michael
中科院分区：
文献类型：
--
作者：
Braeuer, Alois;Beck, Philipp;Groll, Michael
多酶级联反应负责天然产物的生物合成，是合成化学家的灵感来源。来自中性曲霉的铁- ii / α -酮戊二酸依赖的双加氧酶AsqJ是杰出的，因为它可以立体选择性地催化铁诱导的去饱和反应和苯二氮卓二酮的环氧化反应。有趣的是，酶促形成的环氧螺环将6,7-双环骨架负载到喹诺酮类生物碱4'-甲氧基vi可笑素的6,6-双环支架上，进行非酶重排。在此，我们报告了在缺乏和存在合成底物、代物和中间体的情况下蛋白质的不同晶体结构，这些底物、代物和中间体模拟了这种特殊的双加氧酶的反应周期的各个阶段。
Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The Fe-II/alpha-ketoglutaratedependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferrylinduced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4'-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.