Two relA/spoT homologous genes are involved in the morphological and physiological differentiation of Streptomyces clavuligerus

Abstract

This study is focused on the involvement of the unusual nucleotide (p)ppGpp during the morphological and physiological differentiation of Streptomyces clavuligerus. In particular, the functional and structural elements of two genes encoding the proteins RelA and Rsh were identified. The relA gene encodes an 843 aa protein (RelA), while the rsh gene encodes a 738 aa protein (Rsh). The relA and rsh genes were disrupted by the insertion of a hygromycin resistance gene and an apramycin resistance gene, respectively. The synthesis of ppGpp in the relA gene-disrupted mutant was completely eliminated under conditions of starvation for amino acids, whereas synthesis persisted, but was greatly reduced in the rsh gene-disrupted mutant. The relA gene-disrupted mutant had a bald appearance on agar plate cultures and retarded growth in submerged culture, while the rsh-disrupted mutant was unchanged in growth characteristics relative to the wild-type culture. The production of both clavulanic acid and cephamycin C were completely abolished in the relA-disrupted mutant. Thus, it is concluded that the relA gene rather than rsh is essential for morphological and physiological differentiation in S. clavuligerus and that RelA primarily governs the stringent response of S. clavuligerus to starvation for amino acids.

A New TetR Family Transcriptional Regulator Required for Morphogenesis inStreptomyces coelicolor

“…Overexpression of a cluster could result in an abnormally high level of xanthine in the cells and an elevated level of GTP during the time when ppGpp synthesis is strongest. High levels of ppGpp synthesis that result in depletion of the intracellular GTP pool is normally enough to trigger morphological differentiation in Streptomyces species (15). A large GTP pool could cause an arrest in morphological development, while at the same time increased ppGpp production could cause overproduction of actinorhodin.…”

“…Antibiotic production is restored by overexpression of relA, suggesting that increased levels of ppGpp restore antibiotic production. Streptomyces clavuligerus relA mutants are defective in antibiotic production and are bld under all conditions (15). In S. clavuligerus, ppGpp synthesis is accompanied by depletion of the cellular GTP pool (15).…”

“…Streptomyces clavuligerus relA mutants are defective in antibiotic production and are bld under all conditions (15). In S. clavuligerus, ppGpp synthesis is accompanied by depletion of the cellular GTP pool (15). If, as in E. coli, the XDH encoded by the xdhABC cluster is involved in purine salvage, under starvation conditions such as those that signal the initiation of morphogenesis and antibiotic production in Streptomyces species, induction of purine salvage might be a signal for the initiation of antibiotic production and morphological development.…”

ppGpp Metabolism Is Involved in Heterocyst Development in the Cyanobacterium Anabaena sp. Strain PCC 7120

“…In Sorangium cellulosum So ce56, the Srel mutant is unable to form multicellular fruiting bodies under conditions of nutrient starvation (56). ppGpp also affected secondary metabolite biosynthesis (56)(57)(58).…”

Repression of the Antifungal Activity of Pseudomonas sp. Strain DF41 by the Stringent Response

“…Although the SR has been shown to affect antibiotic production in Streptomyces species (4,11,15,18,19), there is a paucity of knowledge regarding how this global stress response influences biocontrol traits in pseudomonads. The purpose of this study was to investigate the impact of the SR on strain DF41 antifungal compound production.…”