Mutations in a new Streptomyces coelicolor locus which globally block antibiotic biosynthesis but not sporulation

Abstract

Streptomyces coelicolor produces four known antibiotics. To define genetic elements that regulate antibiotic synthesis, we screened for mutations that visibly blocked synthesis of the two pigmented antibiotics and found that the mutant strains which we recovered were of two classes--double mutants and mutants in which all four antibiotics were blocked. The mutations in these multiply blocked strains define a new locus of S. coelicolor which we have named absA. The genetic location of absA, at 10 o'clock, is distinct from the locations of the antibiotic gene clusters and from other known mutations that affect antibiotic synthesis. The phenotype of the absA mutants suggests that all S. coelicolor antibiotic synthesis genes are subject to a common global regulation that is at least in part distinct from sporulation and that absA is a genetic component of the regulatory mechanism.

Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces

“…ACT and RED production levels were assayed using a previously described method (31). As ACT was produced both extracellularly and intracellularly (26), the cultures on the plastic cellophane and the agar were collected for determinations of ACT production.…”

A relA/spoT Homologous Gene from Streptomyces coelicolor A3(2) Controls Antibiotic Biosynthetic Genes

“…In S. coelicolor, several so-called pleiotropic genes outside the biosynthetic clusters have been implicated in the regulation of the multiple antibiotic pathways; mutations in absA (14) and absB (15) completely abolish the biosynthesis of all four antibiotics, from which the production of both pigmented antibiotics is restored by the afsQ1-afsQ2 gene pair in absA but not absB mutants (16). Neither actinorhodine nor undecylprodigiosin (as well as reduced amounts of methylenomycin and CDA) could be detected in afsB mutants (17), which were suppressed by the afsR gene (18,19).…”

Genetic suppression analysis of non-antibiotic-producing mutants of the Streptomyces coelicolor absA locus

“…1(b) further refined mapping of the sab locus to the 10 o'clock region by assessing its linkage to cysA, a marker to which the absA locus is linked (Adamidis et al, 1990 and C5423 (Table 1) were crossed, the sab allele segregated with the cysA15 allele and lay anticlockwise to it, as had been previously observed for absA1-542 (Adamidis et al, 1990).…”

“…Mmy assays were as described by Brian et al (1996). For assay of CDA, low-calcium nutrient agar (Oxoid) with or without added calcium [as Ca(NO $ ) # to 12 mM] was used (Adamidis et al, 1990).…”

“…In one genetic analysis of S. coelicolor antibiotic regulation, some mutations that blocked production of all four known antibiotics (Abs − phenotype, for antibiotic synthesis deficient) were found to define the absA locus (Adamidis et al, 1990). This locus was subsequently shown to encode a two-component signal transduction system (Brian et al, 1996) composed of AbsA1, a homologue of ' orthodox ' histidine kinase sensor-transmitter proteins, and AbsA2, a putative DNA-binding response regulator with the amino acid sequences conserved in ' orthodox ' response-regulator proteins (Parkinson, 1995 ;Stock et al, 1995).…”