1997
DOI: 10.1128/jb.179.5.1796-1804.1997
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Abstract: In an effort to characterize the diversity of mechanisms involved in cellular self-protection against the antitumor antibiotic mitomycin C (MC), DNA fragments from the producing organism (Streptomyces lavendulae) were introduced into Streptomyces lividans and transformants were selected for resistance to the drug. Subcloning of a 4.0-kb BclI fragment revealed the presence of an MC resistance determinant, mrd. Nucleotide sequence analysis identified an open reading frame consisting of 130 amino acids with a pre… Show more

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Cited by 40 publications
(40 citation statements)
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References 37 publications
(40 reference statements)
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“…OF008 was identified as M. morganii (9), while the identity of OF013 remained ambiguous (9). they produce because they contain a resistance gene as part of the biosynthetic cluster (19). Therefore, one explanation for our finding that the aerobic bacteria obtained from oil fly larvae are predominantly Providencia and Acinetobacter species (9) is that these bacteria derive a selective advantage by excreting antibiotics that inhibit other microorganisms.…”
Section: Resultsmentioning
confidence: 86%
“…OF008 was identified as M. morganii (9), while the identity of OF013 remained ambiguous (9). they produce because they contain a resistance gene as part of the biosynthetic cluster (19). Therefore, one explanation for our finding that the aerobic bacteria obtained from oil fly larvae are predominantly Providencia and Acinetobacter species (9) is that these bacteria derive a selective advantage by excreting antibiotics that inhibit other microorganisms.…”
Section: Resultsmentioning
confidence: 86%
“…In previous work that led to the identification of MRD as a MC-binding protein, relatively small amounts of protein and substrates (MC, NADH) were used in the in vitro DNA protection assay (7). Although this assay was sensitive enough to detect the protection of DNA from MC-mediated cross-linking, it was not suitable for the detection of potential enzymatic reaction products.…”
Section: Resultsmentioning
confidence: 99%
“…One locus (mcrA), which is located outside of the MC biosynthetic gene cluster, encodes a protein (MCRA) that reoxidizes the reductively activated MC species to the prodrug through a redox relay mechanism (5, 6). Two other loci (mrd and mct) were found within the MC biosynthetic gene cluster and encode a small soluble protein (MRD) and a membrane-associated protein (MCT), respectively (7,8). Whereas MCT has extensive amino acid sequence similarity with several actinomycete antibiotic export proteins, MRD does not significantly resemble any previously characterized protein.…”
Section: Self-protection In the Mitomycin C (Mc)-producing Microorganismmentioning
confidence: 99%
See 1 more Smart Citation
“…The use of multiple resistance mechanisms against a single toxic product is not uncommon (10). Streptomyces lavendulae, for example, protects itself against the deleterious effects of mitomycin via three distinct modes: drug inactivation by a flarin adenine dinucleotide-dependent oxidoreductase (34), drug export (51), and drug sequestration (52). That S. coelicolor employs multiple mechanisms to prevent self-destruction by Act would account for the fact that the actII-ORF2/ORF3 actVA-ORF1 triple mutant (which is defective in exporting Act) is viable (5), as is the soxR mutant.…”
Section: Discussionmentioning
confidence: 99%