C(sp3)−H Hydroxylation in Diiron β-Hydroxylase CmlA Transpires by Amine-Assisted O2 Activation Avoiding FeIV2O2 Species
Dr. Jiarui Lu
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Department of Chemistry, Renmin University of China, Beijing, 100872 China
School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorProf. Dr. Wenzhen Lai
Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Hui Chen
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorDr. Jiarui Lu
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Department of Chemistry, Renmin University of China, Beijing, 100872 China
School of Medical Engineering, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorProf. Dr. Wenzhen Lai
Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Hui Chen
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China
Search for more papers by this authorAbstract
Through QM/MM modeling, we discovered that C(sp3)−H β-hydroxylation in the diiron hydroxylase CmlA transpires by traceless amine-assisted O2 activation. Different from the canonical diiron hydroxylase sMMO, this aliphatic-amine-assisted O2 activation avoids generating the high-valent diferryl FeIV2O2 species, but alternatively renders a diferric FeIII2O species as the reactive oxidant. From this unprecedented O2 activation mode, the derived C(sp3)−H hydroxylation mechanism in CmlA also differs drastically from the toluene aromatic C(sp2)−H hydroxylation in the diiron hydroxylase T4MO. This substrate-modulated O2 activation in CmlA has rich mechanistic implications for other diiron hydroxylases with an amine group adjacent to the C−H bond under hydroxylation in substrates, such as hDOHH. Furthermore, the adapted coordination environment of the diiron cofactor upon O2 binding in CmlA opens up more structural and mechanistic possibilities for O2 activation in non-heme diiron enzymes.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
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