Gamma-butyrolactones (GBLs) produced by several Streptomyces species have been shown to serve as quorum-sensing signaling molecules for activating antibiotic production. The GBL system of Streptomyces chattanoogensis L10, a producer of antifungal agent natamycin, consists of three genes: scgA, scgX, and scgR. Both scgA and scgX contribute to GBL production, while scgR encodes a GBL receptor. ⌬scgA and ⌬scgX mutants of S. chattanoogensis behaved identically: they had a growth defect in submerged cultures and delayed or abolished the morphological differentiation and secondary metabolites production on solid medium. ScgR could bind to the promoter region of scgA and repress its transcription. Moreover, scgA seems also to be controlled by a GBL-mediated negative-feedback system. Hence, it is apparent that GBL biosynthesis is tightly controlled to ensure the correct timing for metabolic switch. An additional direct ScgR-target gene gbdA was identified by genomic SELEX and transcriptional analysis. Comparative proteomic analysis between L10 and its ⌬scgA mutant revealed that the GBL system affects the expression of more than 50 proteins, including enzymes involved in carbon uptake system, primary metabolism, and stress response, we thus conclude that scgR-scgA-scgX constitute a novel GBL regulatory system involved in nutrient utilization, triggering adaptive responses, and finally dictating the switch from primary to secondary metabolism.
Quorum sensing (QS) is a cell-cell communication processin which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density and synchronize community behavior through regulation of their gene expression in response to changes in cell density. Acyl homoserine lactones (AHLs) are a major class of autoinducers used by Gram-negative proteobacteria for intraspecies quorum sensing (23) and has been studied intensively over the past decade. Streptomyces, probably as well as its related genera, use ␥-butyrolactones (2,3-di-substituted-␥-butyrolactones) as autoinducers, the chemical structure of which is similar to that of AHLs except for the carbon side chain (31). In addition, other signal molecules, such as PI factor [2,3-diamino-2,3-bis(hydroxymethyl)-1,4-butanediol] and AHFCAs (2-alkyl-4-hydroxymethylfuran-3-carboxylic acids), have been described to play a similar role to that of GBLs in Streptomyces (6, 26).Streptomycetes are Gram-positive soil bacteria that undergo a developmental program that leads to sporulating aerial hyphae. They are also characterized by a complex secondary metabolism, which makes them the largest antibiotic-producing genus, producing over two-thirds of the clinically used antibiotics of natural origin. The ␥-butyrolactone (GBL) system of Streptomyces, typically consisting of a GBL synthase and a cognate receptor, is drawing more attention because of its close association with production of several antibiotics (31). Currently, there are four such systems with a known GBL and receptor, including the ...