Institute for Theoretical Chemistry, University of Stuttgart, Pfaffenwaldring 55, 70569, Stuttgart, Germany.
Angew Chem Int Ed Engl. 2016 Jan 18;55(3):1168-72. doi: 10.1002/anie.201506363. Epub 2015 Nov 24.
Salicylate 1,2-dioxygenase (SDO) is the first enzyme to be discovered to catalyze the oxidative cleavage of a monohydroxylated aromatic compound, namely salicylate, instead of the well-known electron-rich substrates. We have investigated the mechanism of dioxygen activation in SDO by QM/MM calculations. Our study reveals that the non-heme Fe(II) center in SDO activates salicylate and O2 synergistically through a strong covalent interaction to facilitate the reductive cleavage of O2. A covalent salicylate-Fe(II) -O2 complex is the reactive oxygen species in this case, and its electronic structure is best described as being between the two limiting cases, Fe(II)-O2 and Fe(II)-O2˙(-), with partial electron transfer from the activated salicylate to O2 via the Fe center. Thus SDO employs a synergistic strategy of substrate and oxygen activation to carry out the catalytic reaction, which is unprecedented in the family of iron dioxygenases. Moreover, O2 activation in SDO happens without the assistance of a proton source. Our study essentially shows a new mechanistic possibility for O2 activation.
水杨酸 1,2-双加氧酶（SDO）是第一个被发现能够催化单羟基芳族化合物（即水杨酸）氧化裂解的酶，而不是众所周知的富电子底物。我们通过量子力学/分子力学（QM/MM）计算研究了 SDO 中双氧活化的机制。我们的研究表明，SDO 中的非血红素 Fe(II)中心通过强共价相互作用协同激活水杨酸和 O2，促进 O2 的还原裂解。在这种情况下，一个共价的水杨酸-Fe(II)-O2 配合物是反应性氧物种，其电子结构最好被描述为处于两个极限情况之间，Fe(II)-O2 和 Fe(II)-O2˙(-)，通过 Fe 中心从活化的水杨酸向 O2 转移部分电子。因此，SDO 采用协同的底物和氧活化策略来进行催化反应，这在铁双加氧酶家族中是前所未有的。此外，SDO 中的 O2 活化不需要质子源的辅助。我们的研究本质上展示了一种新的 O2 活化的机制可能性。
