The pyridine ring of NAD is formed by a nonenzymatic pericyclic reaction
The pyridine ring of NAD is formed by a nonenzymatic pericyclic reaction
复制标题
DOI：
10.1021/ja0446395
复制
发表时间：
2005-01-26
影响因子：
15
通讯作者：
Begley, TP
中科院分区：
文献类型：
--
作者：
Colabroy, KL;Begley, TP
The biosynthesis of quinolinate3, the precursor to the pyridine ring of NAD, is still poorly understood. Two pathways have been identified, one involving the direct formation of quinolinic acid from aspartate and dihydroxyacetone phosphate, the other requiring a five-step degradation of tryptophan. The final step in this degradation is catalyzed by the non-heme Fe(II)-dependent enzyme 3-hydroxyanthranilate-3,4-dioxygenase (HAD). This enzyme catalyzes the oxidative ring opening of 3-hydroxyanthranilate (1) to 2-amino-3-carboxymuconic semialdehyde (ACMS,2) which then cyclizes to quinolinate (3). In this communication, we demonstrate the following: (1) cyclization of ACMS to3is not HAD catalyzed, (2) the most stable form of ACMS in solution is an all trans isomer which undergoes facile cis to trans isomerization about the C2−C3 and C4−C5 double bonds via transient formation of its enol tautomer (6), (3) a model study on the ring opening ofN,N-dimethylcarbamoylpyridinium with hydroxide and methoxide suggests that the cyclization of ACMS occurs by an electrocyclization reaction of its enol tautomer6. Thus, the biosynthesis of quinolinic acid, by the tryptophan pathway, is likely to be a member of a growing family of natural products whose biosynthesis involves a pericyclic reaction.
