A recently characterized cytochrome P450 isozyme GcoA activates lignin components through a selective O‐demethylation or alternatively an acetal formation reaction. These are important reactions in biotechnology and, because lignin is readily available; it being the main component in plant cell walls. In this work we present a density functional theory study on a large active site model of GcoA to investigate syringol activation by an iron(IV)‐oxo heme cation radical oxidant (Compound I) leading to hemiacetal and acetal products. Several substrate‐binding positions were tested and full energy landscapes calculated. The study shows that substrate positioning determines the product distributions. Thus, with the phenol group pointing away from the heme, an O‐demethylation is predicted, whereas an initial hydrogen‐atom abstraction of the weak phenolic O‐H group would trigger a pathway leading to ring‐closure to form acetal products. Predictions on how to engineer P450 GcoA to get more selective product distributions are given.

中文翻译：

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木质素通过细胞色素P450酶的生物降解：对GcoA激活的丁香酚的计算研究。

最近表征的细胞色素P450同工酶GcoA通过选择性的O-去甲基化或乙缩醛形成反应激活木质素成分。这些是生物技术中的重要反应，因为木质素很容易获得。它是植物细胞壁的主要成分。在这项工作中，我们对GcoA的大型活性位点模型进行了密度泛函理论研究，以研究丁香酚被铁（IV）-氧代血红素阳离子自由基氧化剂（化合物I）活化而生成半缩醛和乙缩醛产物。测试了多个底物结合位置，并计算了全部能量分布。研究表明，基材的位置决定了产品的分布。因此，在酚基远离血红素的情况下，O可以预测去甲基化，而弱酚O-H基团的最初氢原子抽象将触发导致闭环形成缩醛产物的途径。给出了如何设计P450 GcoA以获得更多选择性产品分配的预测。