1887

Abstract

Antibiotic production in can be activated by introducing certain mutations () into the gene that confer resistance to rifampicin. Working with the most typical () mutant strain, KO-417, the mutation was characterized. The mutation was shown to be responsible for activating antibiotic production and for reducing the growth rate of strain KO-417, as demonstrated by gene-replacement experiments. Gene-expression analysis revealed that introduction of into elevates expression of the pathway-specific regulatory gene - to nearly the same level seen in . The effect on antibiotic production was still evident in the genetic background of , indicating that the mutation can provoke its effect without depending on ppGpp. Accompanying the restoration of antibiotic production, mutants also exhibited a lower rate of RNA synthesis compared to the parental strain when grown in a nutritionally rich medium, suggesting that the mutant RNA polymerases may behave like ’stringent’ RNA polymerases. These results indicate that the mutation can alter the gene-expression pattern independent of ppGpp. The impaired growth of strain KO-417 () was largely restored by introducing the second mutation () just adjacent to the position. Proteome analysis using two-dimensional PAGE revealed that the mutant strain KO-418 () displayed a temporal burst of expression especially of two enzymes, glutamine synthetase (type II) and oxidoreductase, during the late growth phase.

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2002-11-01
2022-01-19
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