The Expanding Role of Methyl-Coenzyme M Reductase in the Anaerobic Functionalization of Alkanes
The Expanding Role of Methyl-Coenzyme M Reductase in the Anaerobic Functionalization of Alkanes
复制标题
甲基辅酶 M 还原酶在烷烃厌氧功能化中的扩展作用
DOI：
10.1021/acs.biochem.9b00859
复制
发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Booker, Squire J.
中科院分区：
文献类型：
--
作者：
Miller, Danielle V.;Booker, Squire J.
由于必须除去的氢的酸性极低，这些反应仅由自由基介导的过程催化，需要裂解C-H键，其均裂键离解能高达105 kcal/mol。[1]在有氧条件下，酶利用广谱的金属辅因子，将氧的还原与生成一种有效的氧化剂结合起来，这种氧化剂可以通过夺取目标氢原子（H·）来裂解未活化的C-H键。1在缺氧条件下，选择更加有限。直到最近，人们认为，除甲烷外，烷烃主要通过富马酸加成代谢，得到烷基琥珀酸酯，尽管最近描述了其他不太好表征的系统。2这些烷基琥珀酸脱氢酶是甘氨酰自由基酶（GRES），其携带稳定的甘氨酰自由基辅因子，该辅因子可逆地产生蛋白质半胱氨酰自由基，该蛋白质半胱氨酰自由基从底物中提取靶H·。甘氨酰自由基辅因子由甘氨酰自由基活化酶安装，所述甘氨酰自由基活化酶是自由基S-腺苷甲硫氨酸（SAM）酶，其催化SAM还原裂解为5′-脱氧腺苷5′-自由基（5′-dA·）。5′-dA·通过从GRE的目标甘氨酰残基立体选择性地提取H·来产生甘氨酰自由基。1
Because of the extreme low acidity of the hydrogens that must be removed, these reactions are catalyzed exclusively by radical-mediated processes, necessitating the cleavage of C− H bonds exhibiting homolytic bond-dissociation energies as high as 105 kcal/mol. 1 Under oxic conditions, enzymes employ a broad spectrum of metallocofactors that couple the reduction of oxygen to the generation of a potent oxidant that can cleave unactivated C− H bonds by abstracting target hydrogen atoms (H•). 1 Under anoxic conditions, the choices are more limited. Until recently, it was believed that, with the exception of methane, alkanes were metabolized primarily through fumarate addition to afford alkylsuccinates, although other less wellcharacterized systems have recently been described. 2 These alkylsuccinate synthases are glycyl radical enzymes (GREs), which carry a stable glycyl radical cofactor that reversibly generates a protein cysteinyl radical that abstracts a target H• from a substrate. The glycyl radical cofactors are installed by glycyl radical activases, which are radical S-adenosylmethionine (SAM) enzymes that catalyze the reductive cleavage of SAM to a 5′-deoxyadenosyl 5′-radical (5′-dA•). The 5′-dA• generates the glycyl radical by stereoselectively abstracting H• from a target glycyl residue of a GRE. 1