Wu H C, Lai J S, Hayashi S, Giam C Z
Biophys J. 1982 Jan;37(1):307-15. doi: 10.1016/S0006-3495(82)84679-1.
Globomycin-resistant mutants of Escherichia coli have been isolated and partially characterized. Approximately 2-5% of these mutants synthesize structurally altered Braun's lipoprotein. The majority of these mutants contain unprocessed and unmodified prolipoprotein. One mutant is found to contain modified, processed, but structurally altered lipoprotein. Mutants containing lipid-deficient prolipoprotein or lipoprotein also show increased resistance to globomycin. These results suggest that the inhibition of processing of modified prolipoprotein by globomycin may require fully modified prolipoprotein as the biochemical target of this novel antibiotic. Our failure to isolate mutant containing cleaved but unmodified lipoprotein among globomycin-resistant mutants is consistent with the possibility that modification of prolipoprotein precedes the removal of signal sequence by a unique signal peptidase. Recent evidence indicates that the minor lipoproteins in the cell envelope of E. coli are also synthesized as lipid-containing prolipoproteins and the processing of these prolipoproteins is inhibited by globomycin. These results suggest the existence of modifying enzymes in E. coli which would transfer glyceryl and fatty acyl moieties to cysteine residues located in the proper sequences of the precursor proteins. This speculation is confirmed by our demonstration that Bacillus licheniformis penicillinase synthesized in E. coli as well as in B. licheniformis is a lipoprotein containing glyceride-cysteine at its NH2-terminus.
已分离出大肠杆菌的抗球霉素突变体并对其进行了部分特性分析。这些突变体中约2 - 5%合成结构改变的 Braun脂蛋白。这些突变体中的大多数含有未加工和未修饰的前脂蛋白。发现一个突变体含有修饰、加工但结构改变的脂蛋白。含有脂质缺陷型前脂蛋白或脂蛋白的突变体也显示出对球霉素的抗性增加。这些结果表明，球霉素对修饰前脂蛋白加工的抑制可能需要完全修饰的前脂蛋白作为这种新型抗生素的生化靶点。我们在抗球霉素突变体中未能分离出含有裂解但未修饰脂蛋白的突变体，这与前脂蛋白修饰先于由独特信号肽酶去除信号序列的可能性是一致的。最近的证据表明，大肠杆菌细胞膜中的次要脂蛋白也以前体脂蛋白形式合成，且这些前体脂蛋白的加工受到球霉素的抑制。这些结果表明大肠杆菌中存在修饰酶，这些酶会将甘油基和脂肪酰基部分转移到位于前体蛋白适当序列中的半胱氨酸残基上。我们证明在大肠杆菌以及地衣芽孢杆菌中合成的地衣芽孢杆菌青霉素酶是一种在其NH2末端含有甘油酯 - 半胱氨酸的脂蛋白，这证实了这一推测。
