Identification and characterization ofStreptomyces flavogriseusNJ-4 as a novel producer of actinomycin D and holomycin

Abstract

This paper is the first public report thatStreptomyces flavogriseuscan produce both actinomycin D and holomycin. The actinomycete strain NJ-4 isolated from the soil of Nanjing Agricultural University was identified asS. flavogriseus. ThisS. flavogriseusstrain was found for the first time to produce two antimicrobial compounds that were identified as actinomycin D and holomycin. GS medium, CS medium and GSS medium were used for the production experiments. All three media supported the production of actinomycin D, while holomycin was detected only in GS medium and was undetectable by HPLC in the CS and GSS media. The antimicrobial activity againstB. pumilus,S. aureus,Escherichia coli,F. moniliforme,F. graminearumandA. nigerwas tested using the agar well diffusion method. Actinomycin D exhibited strong antagonistic activities against all the indicator strains. Holomycin exhibited strong antagonistic activities againstB. pumilus,S. aureusandE. coliand had antifungal activity againstF. moniliformeandF. graminearumbut had no antifungal activity againstA. niger. The cell viability was determined using an MTT assay. Holomycin exhibited cytotoxic activity against A549 lung cancer cells, BGC823 gastric cancer cells and HepG2 hepatocellular carcinoma cells. The yield of actinomycin D fromS. flavogriseusNJ-4 was 960 mg/l.S. flavogriseusNJ-4 exhibits a distinct capability and has the industrial potential to produce considerable yields of actinomycin D under unoptimized conditions.