Advances in Fe(II)/2-ketoglutarate-dependent dioxygenase-mediated C–H bond oxidation for regioselective and stereoselective hydroxyl amino acid synthesis: from structural insights into practical applications

Xiaoran Jing, Huan Liu, Yao Nie, Yan Xu

Systems Microbiology and Biomanufacturing ›› 2021, Vol. 1 ›› Issue (3) : 275-290.

Systems Microbiology and Biomanufacturing ›› 2021, Vol. 1 ›› Issue (3) : 275-290. DOI: 10.1007/s43393-021-00025-z
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Advances in Fe(II)/2-ketoglutarate-dependent dioxygenase-mediated C–H bond oxidation for regioselective and stereoselective hydroxyl amino acid synthesis: from structural insights into practical applications

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Abstract

The asymmetric hydroxylation of inactive carbon atoms in organic compounds remains an important reaction in the industrial synthesis of valuable chiral compounds. Fe(II) and 2-ketoglutarate-dependent dioxygenases (Fe/2-kg DOs) are the largest known subgroups of mononuclear nonheme-Fe(II)-dependent oxygenases, catalyzing various oxidation reactions of C–H bonds. Recent developments in Fe/2-kg DO-related researches have coupled concepts from bioinformatics, synthetic biology, and computational biology to establish effective biotransformation systems. The most well-studied and characterized activity of the Fe/2-kg DOs is substrate hydroxylation, with regard to which mechanistic studies involving the Fe center assist in engineering the protein frameworks of these enzymes to obtain the desired catalytic enhancements. Amino acids are typical substrates of Fe/2-kg DOs and are usually converted into hydroxyl amino acids, which are widely used as intermediates in pharmaceutical and fine chemical industries. Herein, we have reviewed prior structural and mechanistic studies on Fe/2-kg DOs, as well as studies on the Fe/2-kg DO-mediated selective C–H oxidation process for selective hydroxyl amino acid synthesis, which will further our journey along the promising path of building complexity via C–H bond oxidation. Further, new bioinformatics techniques should be adopted with structure-based protein rational design to mine sequence databases and shrink mutant libraries to produce a diverse panel of functional Fe/2-kg DOs capable of catalyzing targeted reactions.

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Xiaoran Jing, Huan Liu, Yao Nie, Yan Xu. Advances in Fe(II)/2-ketoglutarate-dependent dioxygenase-mediated C–H bond oxidation for regioselective and stereoselective hydroxyl amino acid synthesis: from structural insights into practical applications. Systems Microbiology and Biomanufacturing, 2021, 1(3): 275‒290 https://doi.org/10.1007/s43393-021-00025-z
Funding
Financial supports from the National Natural Science Foundation of China,(No. 21676120); the 111 Project,(No. 111-2-06); the High-End Foreign Experts Recruitment Program,(No. G20190010083); the Program for Advanced Talents within Six Industries of Jiangsu Province,(No. 2015-NY-007); the Fundamental Research Funds for the Central Universities,(No. JUSRP51504); the Postgraduate Research & Practice Innovation Program of Jiangsu Province,(No. KYCX19_1833); the Program for the Key Laboratory of Enzymes of Suqian,(No. M201803); the National First-Class Discipline Program of Light Industry Technology and Engineering,(No. LITE2018-09)

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