Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Abstract

SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008

“…The initiation of antibiotic biosynthesis is controlled at several levels genetically (Liu et al, 2013). The most basic and specific control involves genes encoding regulators that work only on one biosynthetic pathway.…”

JadX is a Disparate Natural Product Binding Protein

“…It was found that 15 N-JadX bound Cm at both pH values, with minimal loss in signal intensities ( Figure S19). With Water-LOGSY results comparable at pH 6.6 and 7.6, a series of 1 curve ( Figure 6D) that was fit using nonlinear regression (Equation S2). 48 The measured K d value of 232 μM was lower than that observed with the WaterLOGSY methodology and significantly tighter than the nonspecific binding 48 we have recently observed for JdDS interactions with a series of unrelated enzymes.…”

A gene cluster for the biosynthesis of moenomycin family antibiotics in the genome of teicoplanin producer Actinoplanes teichomyceticus

“…In contrast to the moe genes, the tchm genes do not contain TTA codons, which are known to limit moenomycin production at the translational level, in their coding sequences (Makitrynskyy et al, 2013). In general, tRNA Leu UAA (encoded by bldA gene) is an important and widespread regulatory switch in Streptomycetes Chandra and Chater 2008;Liu et al 2013). It is likely that the tchm cluster is not subject to direct bldA control.…”