Kurtov D, Kinghorn J R, Unkles S E
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Mol Gen Genet. 1999 Aug;262(1):115-20. doi: 10.1007/s004380051065.
Ketopantoate hydroxymethyltransferase, which is encoded by the panB gene in the lower eukaryote Aspergillus nidulans, is essential for the biosynthesis of coenzyme A, while the pathway intermediate 4'-phosphopantetheine is required for penicillin production. Ketopantoate hydroxymethyltransferase could also serve as a target for anti-fungal drugs, since it is not present in mammals. Clones of panB were identified by complementation of the corresponding mutant, and the DNA sequence of the gene was determined. The fungal panB gene encodes a predicted protein of molecular mass 37.7 kDa, containing two short sequence motifs, LeuValGlyAspSer and GlyIleGlyAlaGly, that are completely conserved between prokaryotic and eukaryotic homologues. The mutation panB100 was found to result in deletion of Gly-168, the last glycine within the latter conserved motif. Analysis by gel filtration suggests that the fungal PanB protein can be expressed in Escherichia coli as an active octameric enzyme. The panB transcript is present in low abundance and, most probably, a small increase in transcript levels occurs in the absence of exogenous pantothenate.
泛酮酸羟甲基转移酶由低等真核生物构巢曲霉中的panB基因编码，对辅酶A的生物合成至关重要，而途径中间体4'-磷酸泛酰巯基乙胺是青霉素生产所必需的。泛酮酸羟甲基转移酶也可作为抗真菌药物的靶点，因为它在哺乳动物中不存在。通过相应突变体的互补鉴定出panB克隆，并测定了该基因的DNA序列。真菌panB基因编码一个预测分子量为37.7 kDa的蛋白质，包含两个短序列基序，LeuValGlyAspSer和GlyIleGlyAlaGly，在原核和真核同源物之间完全保守。发现突变体panB100导致后者保守基序中最后一个甘氨酸Gly-168缺失。凝胶过滤分析表明，真菌PanB蛋白可以在大肠杆菌中作为一种活性八聚体酶表达。panB转录本丰度较低，在外源泛酸不存在的情况下，转录水平很可能会有小幅增加。
