“Pseudo” γ-Butyrolactone Receptors Respond to Antibiotic Signals to Coordinate Antibiotic Biosynthesis

• Published in: The Journal of biological chemistry 2010-08, Vol.285 (35), p.27440-27448
• Main Authors: Xu, Gangming, Wang, Juan, Wang, Linqi, Tian, Xiuyun, Yang, Haihua, Fan, Keqiang, Yang, Keqian, Tan, Huarong
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - pharmacology; Antibiotic Biosynthesis; Antibiotics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Regulation; Genetics; Ligand; Ligand-binding Protein; Metabolic Regulation; Microbiology; Protein Binding - drug effects; Protein Binding - physiology; Receptors; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Streptomyces coelicolor - genetics; Streptomyces coelicolor - metabolism; γ-Butyrolactone Receptor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.143081

In actinomycetes, the onset of secondary metabolite biosynthesis is often triggered by the quorum-sensing signal γ-butyrolactones (GBLs) via specific binding to their cognate receptors. However, the presence of multiple putative GBL receptor homologues in the genome suggests the existence of an alternative regulatory mechanism. Here, in the model streptomycete Streptomyces coelicolor, ScbR2 (SCO6286, a homologue of GBL receptor) is shown not to bind the endogenous GBL molecule SCB1, hence designated “pseudo” GBL receptor. Intriguingly, it could bind the endogenous antibiotics actinorhodin and undecylprodigiosin as ligands, leading to the derepression of KasO, an activator of a cryptic type I polyketide synthase gene cluster. Likewise, JadR2 is also a putative GBL receptor homologue in Streptomyces venezuelae, the producer of chloramphenicol and cryptic antibiotic jadomycin. It is shown to coordinate their biosynthesis via direct repression of JadR1, which activates jadomycin biosynthesis while repressing chloramphenicol biosynthesis directly. Like ScbR2, JadR2 could also bind these two disparate antibiotics, and the interactions lead to the derepression of jadR1. The antibiotic responding activities of these pseudo GBL receptors were further demonstrated in vivo using the lux reporter system. Overall, these results suggest that pseudo GBL receptors play a novel role to coordinate antibiotic biosynthesis by binding and responding to antibiotics signals. Such an antibiotic-mediated regulatory mechanism could be a general strategy to coordinate antibiotic biosynthesis in the producing bacteria.