Effect of Actinomycin D Isolated From the Cultured Broth of Marine Streptomyces spp. on Cell Division Protein FtsZ
Phennapa Charoenwiwattanakij, Jaturong Pratuangdejkul, Sumet chongruchiroj, Khanit Suwanborirux, Chitti Thawai, Jiraporn Chingunpitak and Veena Satitpatipan* Author for corresponding; e-mail address: veena.nuk@mahidol.ac.th
Volume: Vol.47 No.3 (May 2020)
Research Article
DOI:
Received: 18 September 2019, Revised: -, Accepted: 5 Febuary 2020, Published: -
Citation: Charoenwiwattanakij P., Pratuangdejkul J., Chongruchiroj S., Suwanborirux K., Thawai C., Chingunpitak J., et al., Effect of Actinomycin D Isolated From the Cultured Broth of Marine Streptomyces spp. on Cell Division Protein FtsZ, Chiang Mai Journal of Science, 2020; 47(3): 362-377.
Abstract
In the course of our investigation on antibacterial substances with FtsZ inhibitory effect, actinomycin D was isolated from the ethyl acetate extract of Streptomyces sp. LT3-17. The compound showed antibacterial activities. The MIC values of actinomycin D against Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus DMST 20654, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were 3.13, 0.39, 0.10, 300.00, and 500.00 μg/mL, respectively. The morphology study of E. coli JW0093 treated with the compound showed inhibitory effect on cell elongation. The inhibition of FtsZ activity by actinomycin D was shown as the inhibition of GTPase activity with IC50 value, 20.06 μM. The polymerization of E. coli FtsZ protein (EcFtsZ) treated with 0.01 μM actinomycin D showed the degree of polymerization ratio was less than 1.0 indicating the inhibitory potential of actinomycin D on FtsZ polymerization. In silico study was performed to predict binding mode of actinomycin D into nucleotide binding pocket of the homology model of EcFtsZ protein. From the results of these experiments, the isolation and elucidation methods of actinomycin D as well as its novel mechanism as FtsZ inhibitors have been discovered.