Two overlapping antiparallel genes encoding the iron regulator DmdR1 and the Adm proteins control sidephore and antibiotic biosynthesis in Streptomyces coelicolor A3(2)

Abstract

The dmdR1 gene of Streptomyces coelicolor encodes an important regulator of iron metabolism. An antiparallel gene (adm) homologous to a development‐regulated gene of Streptomyces aureofaciens has been found to overlap with dmdR1. Both proteins DmdR1 and Adm are formed in solid and liquid cultures of S. coelicolor A3(2). The purpose of this study was to assess possible interaction between the products of these two antiparallel genes. Two mutants with stop codons resulting in arrested translation of either DmdR1 or Adm were obtained by gene replacement and compared with a deletion mutant (ΔdmdR1/adm) that was defective in both genes. The deletion mutant was unable to form either protein, did not sporulate and lacked desferrioxamine, actinorhodin and undecylprodigiosin biosynthesis; biosynthesis of these compounds was recovered by complementation with dmdR1/adm genes. The mutant in which formation of Adm protein was arrested showed normal levels of DmdR1, lacked Adm and over‐produced the antibiotics undecylprodigiosin and actinorhodin (in MS medium), suggesting that Adm plays an important role in secondary metabolism. The mutant in which DmdR1 formation was arrested synthesized desferrioxamines in a constitutive (deregulated) manner, and produced relatively normal levels of antibiotics. In conclusion, our results suggest that there is a fine interplay of expression of these antiparallel genes, as observed for other genes that encode lethal proteins such as the toxin/antitoxin systems. The Adm protein seems to have a major effect on the control of secondary metabolism, and its formation is probably tightly controlled, as expected for a key regulator.

Predicting Statistical Properties of Open Reading Frames in Bacterial Genomes

“…It can be hypothesized that such long ORFs might be coding and form overlapping shadow genes. An interesting coincidence might be the fact that the recently described regulatory gene adm overlaps dmdR1 in frame −2 in Streptomyces [25]. Concerning long overlapping ORFs in frame −1, it should be further noted that at least some of these ORFs appear in genes not found to be highly expressed [41].…”

“…Trivial overlaps (<30 codons) exist in basically all bacteria. Up to 30% of the genes of a bacterium may overlap trivially [13], but only few of the shadow genes have been recognized as true genes in bacteria to date (e.g., [21]–[25], [43], [44]). Using the model developed in this study, we could show that the length distribution of shadow genes overlapping annotated genes deviates significantly between model and bacterial genome.…”

“…The former is a homolog of a well-known class of iron regulators, the latter turned out to be involved in the control of secondary metabolites. Both genes overlap except a few base pairs in antiparallel fashion and are about 700 bp in length [25]. Thus, increasing evidence as cited above, from many different unrelated bacteria suggests that overlapping genes are no rare biological oddities.…”

“…For some of the overlapping genes the protein-products have been identified using mass spectrometry [24]. Last but not least, Tunca et al [25] used nicely designed strand specific knock-out mutants to demonstrate a phenotype for both genes of the overlapping gene pair dmdR1/adm . The former is a homolog of a well-known class of iron regulators, the latter turned out to be involved in the control of secondary metabolites.…”

Hierarchical Control on Polyene Macrolide Biosynthesis: PimR Modulates Pimaricin Production via the PAS-LuxR Transcriptional Activator PimM

“…S. natalensis ATCC 27448 was grown for 48 h in YEME medium without sucrose (stationary phase of growth), the cultures were then treated as described elsewhere [48].…”