HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Gomez-Escribano, J. P. Articles by Liras, P. PubMed PubMed Citation Articles by Gomez-Escribano, J. P. Articles by Liras, P. Agricola Articles by Gomez-Escribano, J. P. Articles by Liras, P.

Streptomyces clavuligerus relA-null mutants overproduce clavulanic acid and cephamycin C: negative regulation of secondary metabolism by (p)ppGpp

¹ Área de Microbiología, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, Campus de Vegazana s/n, 24071 León, Spain
² Instituto de Biotecnología (INBIOTEC), Parque Científico de León, Av. Real 1, 24006 León, Spain
³ Department of Molecular Microbiology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK

Correspondence
P. Liras
paloma.liras{at}unileon.es

The (p)ppGpp synthetase gene, relA, of Streptomyces clavuligerus was cloned, sequenced and shown to be located in a genomic region that is highly conserved in other Streptomyces species. relA-disrupted and relA-deleted mutants of S. clavuligerus were constructed, and both were unable to form aerial mycelium or to sporulate, but regained these abilities when complemented with wild-type relA. Neither ppGpp nor pppGpp was detected in the S. clavuligerus relA-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 relA-null mutants with wild-type relA decreased antibiotic yields to approximately wild-type levels. Consistent with these observations, transcription of genes involved in clavulanic acid (ceaS2) or cephamycin C (cefD) production increased dramatically in the relA-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 Streptomyces species of industrial interest.

The GenBank/EMBL/DDBJ accession number for the sequence of the 5.4 kb DNA fragment cloned in this work is AM408890.