title: AllR Controls the Expression of Streptomyces coelicolor Allantoin Pathway Genes.
abstract: Streptomyces species are native inhabitants of soil, a natural environment where nutrients can be scarce and competition fierce. They have evolved ways to metabolize unusual nutrients, such as purines and its derivatives, which are highly abundant in soil. Catabolism of these uncommon carbon and nitrogen sources needs to be tightly regulated in response to nutrient availability and environmental stimulus. Recently, the allantoin degradation pathway was characterized in Streptomyces coelicolor. However, there are questions that remained unanswered, particularly regarding pathway regulation. Here, using a combination of proteomics and genetic approaches, we identified the negative regulator of the allantoin pathway, AllR. In vitro studies confirmed that AllR binds to the promoter regions of allantoin catabolic genes and determined the AllR DNA binding motif. In addition, effector studies showed that allantoic acid, and glyoxylate, to a lesser extent, inhibit the binding of AllR to the DNA. Inactivation of AllR repressor leads to the constitutive expression of the AllR regulated genes and intriguingly impairs actinorhodin and undecylprodigiosin production. Genetics and proteomics analysis revealed that among all genes from the allantoin pathway that are upregulated in the allR mutant, the hyi gene encoding a hydroxypyruvate isomerase (Hyi) is responsible of the impairment of antibiotic production.
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR-Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Navone
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR-Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Macagno
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia Evolution of Metabolic Diversity Laboratory, Laboratorio Nacional de Genómica para la Biodiversidad, Cinvestav-IPN, Irapuato, Mexico.
authors.forename: Cuauhtémoc
authors.initials: C
authors.lastname: Licona-Cassani
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Esteban
authors.initials: E
authors.lastname: Marcellin
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Lars K
authors.initials: LK
authors.lastname: Nielsen
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR-Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gramajo
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR-Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina erodriguez@ibr-conicet.gov.ar.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rodriguez
mesh_terms: D000481:Allantoin / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D048372:Streptomyces coelicolor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012097:Repressor Proteins; D000481:Allantoin