Mechanism of CuO nano-particles on stimulating production of actinorhodin in Streptomyces coelicolor by transcriptional analysis

In this research, antibiotic-producing bacteria, Streptomyces coelicolor (S. coelicolor) M145, was exposed to copper oxide (CuO) particles to investigate the effects of nano-particles (NPs) on antibiotic production. Results showed that a higher yield of antibiotics was obtained with smaller particle sizes of CuO NPs. When exposed to 10 mg/L of 40 nm CuO NPs, the maximum amount of actinorhodin (ACT) obtained was 2.6 mg/L after 144 h, which was 2.0-fold greater than that of control. However, the process was inhibited when the concentration of CuO NPs was increased to higher than 20 mg/L. Transcriptome analysis showed that all the genes involved in the ACT cluster were significantly up-regulated after exposure to 10 mg/L NPs, which could be the direct cause of the increase of ACT production. Additionally, some genes related to the generation of acetyl-coA were up-regulated. In this way, CuO NPs led to an increase of secondary metabolites. The mechanism related to these changes indicated that nano-particle‒induced ROS and Cu(2+) played synergetic roles in promoting ACT biosynthesis. This is a first report suggesting that CuO NPs had a significant effect on antibiotic production, which will be helpful in understanding the mechanism of antibiotic production in nature.