The dynamic architecture of the metabolic switch in Streptomyces coelicolor

Abstract

BackgroundDuring the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.ResultsSurprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis.ConclusionsOur study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.

The MreB-Like Protein Mbl ofStreptomyces coelicolorA3(2) Depends on MreB for Proper Localization and Contributes to Spore Wall Synthesis

“…After 48 and 72 h on LB agar, when only substrate mycelium was formed, mreB was expressed but a mbl transcript could not be detected; sco6166 showed the strongest expression. This was in agreement with detailed microarray data from S. coelicolor liquid cultures (38) showing the strong expression of sco6166, intermediate expression of mreB, and only very weak expression of mbl during a period of 40 h (K. Nieselt, personal communication). After 48 h on MS agar, when aerial mycelium already was developed, mreB transcription increased and mbl transcription was detectable at a low level.…”

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

“…Under these circumstances, a transient arrest of growth typically ensues, accompanied by a complex series of changes in global gene expression. Antibiotic production and morphological differentiation may then take place (12,13). Antibiotic production at the industrial level is highly dependent on the fermentation conditions, with the need for a balance between, on one hand, providing nutrients for growth and as precursors for antibiotics and, on the other hand, the repressive effects of some of the most efficient sources of carbon, nitrogen, and phosphate.…”

An Engineered Strong Promoter for Streptomycetes

“…Our previous work indicated that kasOp is rigorously regulated by ScbR and ScbR2; the former is the ␥-butyrolactone (GBL, SCB) receptor in S. coelicolor, whereas ScbR2 shows great similarity to ScbR but could not bind GBL and thus was called a "pseudo"-GBL receptor (31). kasO transcripts are undetectable during rapid growth, but the gene is sharply turned on and off in a small time window at the transition phase (2,30). The regulatory mechanism is most likely determined by the interplay between ScbR and ScbR2 (32).…”

“…he genus Streptomyces is known for its ability to produce antibiotics and for its complex morphology (1,2). It is not only an ideal model to study bacterial differentiation but is also considered a good host for antibiotic production.…”

“…According to previous research, kasO (also known as cpkO and SCO6280), encodes a SARP family regulator and is an activator of a cryptic type I polyketide synthase gene cluster responsible for coelimycin P1 production in S. coelicolor A3 (2,28,29). The upstream region of the kasO promoter (kasOp) spans nearly 400 bp of DNA, and its core promoter sequence is similar to the HrdBrecognized consensus sequence (30) (Fig.…”