Biogenesis of membrane lipoproteins in Escherichia coli.
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.
D000900:Anti-Bacterial Agents; D001407:Bacillus / Q000235:genetics; D010582:Bacteriophage lambda / Q000201:enzymology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000648:ultrastructure; D008074:Lipoproteins / Q000096:biosynthesis*; D008242:Lysogeny / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis; D008954:Models, Biological; D010405:Penicillinase / Q000096:biosynthesis / Q000235:genetics; D010455:Peptides / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008074:Lipoproteins; D008565:Membrane Proteins; D010455:Peptides; C017339:globomycin; D010405:Penicillinase