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A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis

Jennifer Bridwell-Rabb, Aoshu Zhong, He G. Sun, Catherine L. Drennan & Hung-wen Liu

Nature 544, 322–326 (20 April 2017) doi:10.1038/nature21689


コバラミン(ビタミンB12)の入っている酵素についての報告です。
この論文では、オキセタン(環状四員環エーテル)化合物を与える桿菌由来のOxsA、OxsBという酵素についての報告をしています。
デオキシアデノシンが、酸化を受けて縮環が進行するのが面白いです。
ここで、なにがH・を引き抜くのか、我々としては気になるところですが、論文によれば、
S-adenosylmethionine(AdoMet)(下図)の還元によって、メチオニンが脱離することで生じる、メチルラジカルです。



多くの場合、コバラミンはメチル基の転移などの過程に関与するとされているのですが、この酵素の場合、電子移動を補佐するだけで直接基質とはくっつかないようで、この点が新しいのだそうです。
(あまり読んでいないのに、言えませんが、生成するラジカル中間体とくっついたりしてても全然おかしくないと思います。こういうところが、モデルの出番かもしれません。)

ちなみに、このオキセタン化合物は、抗腫瘍、抗菌、抗ウイルス作用が期待されるそうです。DNAポリメラーゼを阻害することが理由だそうです。アデニン部位で水素結合でくっついて、不安定なオキセタン構造が崩れながら、どっかに共有結合をつくるのでしょう。

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