Petersen L, Enos-Berlage J, Downs D M
Department of Bacteriology, University of Wisconsin, Madison 53706.
Genetics. 1996 May;143(1):37-44. doi: 10.1093/genetics/143.1.37.
The first five steps in de novo purine biosynthesis are involved in the formation of the 4-amino-5-hydroxymethyl-2-methyl pyrimidine (HMP) moiety of thiamine. We show here that the first enzyme in de novo purine biosynthesis, PurF, is required for thiamine synthesis during aerobic growth on some but not other carbon sources. We show that PurF-independent thiamine synthesis depends on the recently described alternative pyrimidine biosynthetic (APB) pathway. Null mutations in zwf (encoding glucose-6-dehydrogenase), gnd (encoding gluconate-6-P dehydrogenase), purE (encoding aminoimidazole ribonucleotide carboxylase), and purR (encoding a regulator of gene expression) were found to affect the function of the APB pathway. A model is presented to account for the involvement of these gene products in thiamine biosynthesis via the APB pathway. Results presented herein demonstrate that function of the APB pathway can be prevented either by blocking intermediate formation or by diverting intermediate(s) from the pathway. Strong genetic evidence supports the conclusion that aminoimidazole ribotide (AIR) is an intermediate in the APB pathway.
从头嘌呤生物合成的前五个步骤参与硫胺素4-氨基-5-羟甲基-2-甲基嘧啶（HMP）部分的形成。我们在此表明，从头嘌呤生物合成中的第一种酶PurF，在某些而非其他碳源上有氧生长期间的硫胺素合成中是必需的。我们表明，不依赖PurF的硫胺素合成取决于最近描述的替代嘧啶生物合成（APB）途径。发现zwf（编码葡萄糖-6-脱氢酶）、gnd（编码葡萄糖酸-6-磷酸脱氢酶）、purE（编码氨基咪唑核糖核苷酸羧化酶）和purR（编码基因表达调节剂）中的无效突变会影响APB途径的功能。提出了一个模型来解释这些基因产物通过APB途径参与硫胺素生物合成的情况。本文给出的结果表明，APB途径的功能可以通过阻断中间产物形成或使中间产物从该途径转移来阻止。强有力的遗传学证据支持氨基咪唑核糖核苷酸（AIR）是APB途径中的一种中间产物这一结论。
