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

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 activ-ity 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.

ASPH在肝脏恶性肿瘤发生发展中作用和机制研究进展

天冬氨酰-(天冬酰胺酰)β-羟化酶(ASPH)是α-酮戊二酸依赖性双加氧酶,催化天冬氨酰和天冬酰胺基残基的羟化。ASPH在肝细胞癌和肝内胆管癌中均有表达,对二者的发生和发展有作用。本文主要对ASPH的结构和功能及其作用机制的研究进展进行综述。