Begley T P, Kinsland C, Strauss E
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA.
Vitam Horm. 2001;61:157-71. doi: 10.1016/s0083-6729(01)61005-7.
Coenzyme A (I) and enzyme-bound phosphopantetheine (II) function as acyl carriers and as carbonyl activating groups for Claisen reactions as well as for amide-, ester-, and thioester-forming reactions in the cell. In so doing, these cofactors play a key role in the biosynthesis and breakdown of fatty acids and in the biosynthesis of polyketides and nonribosomal peptides. Coenzyme A is biosynthesized in bacteria in nine steps. The biosynthesis begins with the decarboxylation of aspartate to give beta-alanine. Pantoic acid is formed by the hydroxymethylation of alpha-ketoisovalerate followed by reduction. These intermediates are then condensed to give pantothenic acid. Phosphorylation of pantothenic acid followed by condensation with cysteine and decarboxylation gives 4'-phosphopantetheine. Adenylation and phosphorylation of 4'-phosphopantetheine completes the biosynthesis of coenzyme A. This review will focus on the mechanistic enzymology of coenzyme A biosynthesis in bacteria.
辅酶A(I)和与酶结合的磷酸泛酰巯基乙胺(II)在细胞中作为酰基载体以及克莱森反应(Claisen反应)以及酰胺、酯和硫酯形成反应的羰基活化基团发挥作用。在此过程中,这些辅因子在脂肪酸的生物合成和分解以及聚酮化合物和非核糖体肽的生物合成中起关键作用。辅酶A在细菌中通过九个步骤生物合成。生物合成始于天冬氨酸脱羧生成β-丙氨酸。泛解酸由α-酮异戊酸的羟甲基化反应然后还原反应形成。这些中间体随后缩合生成泛酸。泛酸磷酸化,然后与半胱氨酸缩合并脱羧,生成4'-磷酸泛酰巯基乙胺。4'-磷酸泛酰巯基乙胺的腺苷化和磷酸化完成了辅酶A的生物合成。本综述将聚焦于细菌中辅酶A生物合成的机理酶学。