Grodberg J, Dunn J J
Department of Microbiology, State University of New York at Stony Brook 11794.
J Bacteriol. 1988 Mar;170(3):1245-53. doi: 10.1128/jb.170.3.1245-1253.1988.
Bacteriophage T7 RNA polymerase is stable in Escherichia coli but very susceptible to cleavage by at least one endoprotease after cell lysis. The major source of this endoprotease activity was found to be localized to the outer membrane of the cell. A rapid whole-cell assay was developed to screen different strains for the presence of this proteolytic activity. Using this assay, we identified some common laboratory strains that totally lack the protease. Genetic and Southern analyses of these null strains allowed us to conclude that the protease that cleaves T7 RNA polymerase is OmpT (formerly termed protein a), a known outer membrane endoprotease, and that the null phenotype results from deletion of the OmpT structural gene. A recombinant plasmid carrying the ompT gene enables these deletion strains to synthesize OmpT and converts them to a protease-positive phenotype. The plasmid led to overproduction of OmpT protein and protease activity in the E. coli K-12 and B strains we used, but only weak expression in the E. coli C strain, C1757. This strain-dependent difference in ompT expression was investigated with respect to the known influence of envZ on OmpT synthesis. A small deletion in the ompT region of the plasmid greatly diminishes the amount of OmpT protein and plasmid-encoded protease present in outer membranes. Use of ompT deletion strains for production of T7 RNA polymerase from the cloned gene has made purification of intact T7 RNA polymerase routine. Such strains may be useful for purification of other proteins expressed in E. coli.
噬菌体T7 RNA聚合酶在大肠杆菌中很稳定,但细胞裂解后极易被至少一种内切蛋白酶切割。发现这种内切蛋白酶活性的主要来源定位于细胞的外膜。开发了一种快速全细胞检测方法来筛选不同菌株中这种蛋白水解活性的存在。利用该检测方法,我们鉴定出了一些完全缺乏该蛋白酶的常见实验室菌株。对这些缺失菌株的遗传和Southern分析使我们得出结论,切割T7 RNA聚合酶的蛋白酶是OmpT(以前称为蛋白a),一种已知的外膜内切蛋白酶,并且缺失表型是由OmpT结构基因的缺失导致的。携带ompT基因的重组质粒使这些缺失菌株能够合成OmpT并将它们转变为蛋白酶阳性表型。在我们使用的大肠杆菌K-12和B菌株中,该质粒导致OmpT蛋白和蛋白酶活性过量产生,但在大肠杆菌C菌株C1757中只有微弱表达。针对envZ对OmpT合成的已知影响,研究了ompT表达中这种菌株依赖性差异。质粒ompT区域的一个小缺失极大地减少了外膜中存在的OmpT蛋白和质粒编码蛋白酶的量。使用ompT缺失菌株从克隆基因生产T7 RNA聚合酶已使完整T7 RNA聚合酶的纯化成为常规操作。这样的菌株可能有助于纯化在大肠杆菌中表达的其他蛋白质。