Abstract
The penetration of levallorphan, a synthetic morphinan known to interact with the cytoplasmic membrane of E. coli, is seriously limited by the outer membrane. To select target-resistant mutants rather than outer membrane mutants, a two-step procedure was developed, which involved the selection by penicillin of an "intermediate" parental strain with a decreased penetration barrier and a subsequent positive selection of levallorphan-tolerant pseudo-revertant clones. Unlike the direct selection, this technique yielded various types of mutants in which the morphology, the septation ability, and the growth rate were greatly affected.
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