1887

Abstract

The (p)ppGpp synthetase gene, of was cloned, sequenced and shown to be located in a genomic region that is highly conserved in other species. -disrupted and -deleted mutants of were constructed, and both were unable to form aerial mycelium or to sporulate, but regained these abilities when complemented with wild-type . Neither ppGpp nor pppGpp was detected in the -deletion mutant. In contrast to another study, clavulanic acid and cephamycin C production increased markedly in the mutants compared to the wild-type strain; clavulanic acid production increased three- to fourfold, while that of cephamycin C increased about 2.5-fold. Complementation of the -null mutants with wild-type decreased antibiotic yields to approximately wild-type levels. Consistent with these observations, transcription of genes involved in clavulanic acid () or cephamycin C () production increased dramatically in the -deleted mutant when compared to the wild-type strain. These results are entirely consistent with the growth-associated production of both cephamycin C and clavulanic acid, and demonstrate, apparently for the first time, negative regulation of secondary metabolite biosynthesis by (p)ppGpp in a species of industrial interest.

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2008-03-01
2019-10-15
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