Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2).
Genome sequencing of Streptomyces coelicolor A3(2) revealed an uncharacterized type I polyketide synthase gene cluster (cpk). Here we describe the discovery of a novel antibacterial activity (abCPK) and a yellow-pigmented secondary metabolite (yCPK) after deleting a presumed pathway-specific regulatory gene (scbR2) that encodes a member of the gamma-butyrolactone receptor family of proteins and which lies in the cpk gene cluster. Overproduction of yCPK and abCPK in a scbR2 deletion mutant, and the absence of the newly described compounds from cpk deletion mutants, suggest that they are products of the previously orphan cpk biosynthetic pathway in which abCPK is converted into the yellow pigment. Transcriptional analysis suggests that scbR2 may act in a negative feedback mechanism to eventually limit yCPK biosynthesis. The results described here represent a novel approach for the discovery of new, biologically active compounds.
Gottelt
Marco
M
Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Kerklaan 30, 9751NN Haren, The Netherlands.
Kol
Stefan
S
Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Kerklaan 30, 9751NN Haren, The Netherlands.
Gomez-Escribano
Juan Pablo
JP
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.
Bibb
Mervyn
M
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.
Takano
Eriko
E
Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Kerklaan 30, 9751NN Haren, The Netherlands.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D005810:Multigene Family; D010860:Pigments, Biological / Q000096:biosynthesis*; D048630:Polyketide Synthases / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
C037481:4-butyrolactone receptor; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010860:Pigments, Biological; D011963:Receptors, GABA-A; D048630:Polyketide Synthases