The mthA Mutation Conferring Low-Level Resistance to Streptomycin Enhances Antibiotic Production in Bacillus subtilis by Increasing the S -Adenosylmethionine Pool Size
| Autor: | Shigeo Tojo, Takashi Inaoka, Yoshikazu Hiraga, Ji-Yun Kim, Kozo Ochi, Yukinori Tanaka |
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| Rok vydání: | 2014 |
| Předmět: |
S-Adenosylmethionine
Mutant Articles Dipeptides Bacillus subtilis Biology biology.organism_classification Microbiology Streptomyces Anti-Bacterial Agents Methylthioadenosine nucleosidase Streptomycin Drug Resistance Bacterial Mutation medicine Mutant Proteins Secondary metabolism Overproduction N-Glycosyl Hydrolases Molecular Biology Gene medicine.drug |
| Zdroj: | Journal of Bacteriology. 196:1514-1524 |
| ISSN: | 1098-5530 0021-9193 |
| Popis: | Certain Str r mutations that confer low-level streptomycin resistance result in the overproduction of antibiotics by Bacillus subtilis . Using comparative genome-sequencing analysis, we successfully identified this novel mutation in B. subtilis as being located in the mthA gene, which encodes S -adenosylhomocysteine/methylthioadenosine nucleosidase, an enzyme involved in the S -adenosylmethionine (SAM)-recycling pathways. Transformation experiments showed that this mthA mutation was responsible for the acquisition of low-level streptomycin resistance and overproduction of bacilysin. The mthA mutant had an elevated level of intracellular SAM, apparently acquired by arresting SAM-recycling pathways. This increase in the SAM level was directly responsible for bacilysin overproduction, as confirmed by forced expression of the metK gene encoding SAM synthetase. The mthA mutation fully exerted its effect on antibiotic overproduction in the genetic background of rel + but not the rel mutant, as demonstrated using an mthA relA double mutant. Strikingly, the mthA mutation activated, at the transcription level, even the dormant ability to produce another antibiotic, neotrehalosadiamine, at concentrations of 150 to 200 μg/ml, an antibiotic not produced (rsmG mutation to Streptomyces or the mthA mutation to eubacteria, since many eubacteria have mthA homologues. |
| Databáze: | OpenAIRE |
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