Isolation, characterization, anti-MRSA evaluation, and in-silico multi-target anti-microbial validations of actinomycin X2 and actinomycin D produced by novel Streptomyces smyrnaeus UKAQ_23

Streptomyces smyrnaeus UKAQ_23, isolated from the mangrove-sediment, collected from Jubail,Saudi Arabia, exhibited substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), including non-MRSA Gram-positive test bacteria. The novel isolate, under laboratory-scale conditions, produced the highest yield (561.3 +/- 0.3 mg/kg fermented agar) of antimicrobial compounds in modified ISP-4 agar at pH 6.5, temperature 35 degrees C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K-1 and K-2, were isolated from fermented medium and identified as Actinomycin X-2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X-2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X-2:D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 mu g/disc concentrations. The MIC of Actinomycin X-2 ranged from 1.56-12.5 mu g/ml for non-MRSA and 3.125-12.5 mu g/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X-2 and D, while the penicillin-binding protein-1a, was the least-favorable target-protein. In conclusion, Streptomyces smyrnaeus UKAQ_23 emerged as a promising source of Actinomycin X-2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry.

Automated summary

The new strain Streptomyces smyrnaeus UKAQ_23 isolated from mangrove sediment in Saudi Arabia showed substantial antimicrobial activity against MRSA and non-MRSA Gram-positive test bacteria, and produced a high yield of antimicrobial compounds, including Actinomycin X-2 and Actinomycin D. Actinomycin X-2 exhibited higher antimicrobial activity compared to Actinomycin D, making it a promising candidate for industrial production with potential benefits for the pharmaceutical industry.