1887

Abstract

Peptide deformylation is an essential process in eubacteria. The peptide deformylase Def has been suggested to be an attractive target for antibacterial drug discovery. Some eubacteria including medically important pathogens possess two like genes. Until now, the functionality of both genes has been tested only in with the result that one gene copy was functional. Here, expression of two functional -like gene products in is demonstrated. Besides the gene, which is chromosomally located close to the formyltransferase gene and which was overexpressed and biochemically tested previously, possesses a second -like gene, called . The encoded protein is 32% identical to the gene product. It was shown that either or had to be present for growth of in rich medium (each was individually dispensable). Studies with a / double deletion strain with xylose-inducible copy demonstrated that, besides , the gene is a second cellular target of deformylase inhibitors such as the antibiotic actinonin. The gene products exhibited similar enzymic properties, exemplified by similar inhibition efficacy of actinonin in biochemical assays. Antibiotic susceptibility tests with different deletion strains and Northern analyses indicated that YkrB is probably the predominant deformylase in . It was shown that duplication of the deformylase function does not lead to an increased actinonin-resistance frequency in comparison to mutants carrying only one deformylase gene.

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2001-07-01
2019-10-22
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