Streptomyces RNases - Function and impact on antibiotic synthesis

Abstract

Streptomyces are soil dwelling bacteria that are notable for their ability to sporulate and to produce antibiotics and other secondary metabolites. Antibiotic biosynthesis is controlled by a variety of complex regulatory networks, involving activators, repressors, signaling molecules and other regulatory elements. One group of enzymes that affects antibiotic synthesis in Streptomyces is the ribonucleases. In this review, the function of five ribonucleases, RNase E, RNase J, polynucleotide phosphorylase, RNase III and oligoribonuclease, and their impact on antibiotic production will be discussed. Mechanisms for the effects of RNase action on antibiotic synthesis are proposed.

Keywords: RNA decay; RNA processing; Streptomyces; antibiotic; regulation; ribonuclease.

Figure 1

Overproduction of red (right bar graph) and act (left bar graph) by an rraAS1 null mutant of S. coelicolor. The antibiotics were measured using spectroscopic methods from mycelium harvested at the times indicated on the x-axis of the figures. The antibiotic concentrations were normalized relative to mycelial dry weights. The rightmost part of the figure shows the results of an RT-PCR analysis of the levels of the CSRs, actII-orf4 and redZ in the parental and rraAS1 null mutant strains of S. coelicolor. Reprinted with permission from Seo et al. (2017).

Figure 2

Effects of an rnj null mutation on antibiotic production in S. coelicolor. The top panel (A) shows the temporal progress of act and red production in the parental (M145) and mutant (JSE2301) strains cultured on solid medium that supports antibiotic biosynthesis. pJSE2255 is a plasmid containing the wild type RNase J gene cloned into the streptomycete expression vector, pIJ8600. In the rnj null mutant, act production is suppressed while red is overproduced. The bottom panel (B) shows the levels of cda production in the wild type and parental S. coelicolor strains. The figure shows zones of inhibition produced by cda action against a cda-sensitive bacterial strain, B. subtilis BG267. Reprinted with permission from Pei et al. (2015).

Figure 3

Proposed mechanism for the action of RNases on the transcripts of the various regulatory factors that have been shown to be involved in the regulation and production of antibiotics in Streptomyces. The model proposes that any of the transcript classes shown might be targets for RNase processing or degradation and that the effects of the RNases would then impact antibiotic production.