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

Abstract

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 °C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K1 and K2, were isolated from fermented medium and identified as Actinomycin X2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X2:D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 µg/disc concentrations. The MIC of Actinomycin X2 ranged from 1.56–12.5 µg/ml for non-MRSA and 3.125–12.5 µg/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X2 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 X2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry.

In Vitro and In Silico Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel Streptomyces smyrnaeus Strain UKAQ_23

“…The actinomycete strain, UKAQ_23, was isolated from a mangrove sediment sample collected from Jubail, Saudi Arabia, in 2019 ( Figure 1 ), identified as Streptomyces smyrnaeus strain UKAQ_23, and comprehensively characterized. Our earlier published article has further details about this organism [ 14 ].…”

“…The solid-liquid extraction technique yielded an amorphous, reddish-orange crude antimicrobial extract ( Figure 2 a). TLC showed two major components, K 1 , and K 2 in the crude antimicrobial extract [ 14 ]. As a result, both the compounds were selected for further study.…”

“…The pure components K 1 and K 2 were obtained by using various chromatographic techniques ( Figure 2 b). Additional information on the isolation, purification, and characterization of the actinomycins, X 2 and D, are provided in the previously published article by us [ 14 ].…”

“…Thus, based on their physicochemical and spectroscopic analysis results, the isolated components K 1 and K 2 were identified as actinomycin X 2 and actinomycin D, respectively ( Figure 3 ). Additional information on the elucidation of the structures of the actinomycins, X 2 and D, was provided in a previously published article by us [ 14 ].…”

“…II, Streptomyces flavogriseus NJ-4, Streptomyces MITKK-103, Streptomyces griseoruber , Streptomyces strain M7, Streptomyces sp. HUST012, Streptomyces heliomycini , Streptomyces hydrogenans IB310 produce actinomycin X 2 and actinomycin D, which have provided anti-parasitic and some with anti-leishmanial compounds [ 14 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Several previously published reports specified that actinomycins D, Z3, Z5 have significant antileishmanial activity [ 10 , 11 , 34 ].…”