# Actinomycin Analogs from Soil-Derived Streptomyces sp. PSU-S4-23 with Activity Against MRSA

## TL;DR

A new Streptomyces strain from Thai soil produces actinomycin analogs effective against drug-resistant bacteria like MRSA.

## Contribution

Discovery of a novel Streptomyces strain producing multiple actinomycin analogs with broad antibacterial activity.

## Key findings

- Streptomyces sp. PSU-S4-23 produces actinomycin X2, D, and I analogs as confirmed by LC–MS/MS and molecular networking.
- The strain shows antibacterial activity against MRSA and other pathogens including Pseudomonas aeruginosa and Acinetobacter baumannii.
- Genomic analysis confirms the strain is distinct from its closest relative, S. caeni CGMCC 4.7426T.

## Abstract

Genome-based discovery provides a powerful approach for identifying bioactive natural products. In this study, Streptomyces sp. PSU-S4-23 was isolated from soil collected in southern Thailand. Genome analysis revealed a nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster highly similar to the reference actinomycin D cluster, including canonical NRPS genes and a cytochrome P450 associated with oxidative tailoring. Genomic comparison indicated that this strain is distinct from its closest relative S. caeni CGMCC 4.7426T with ANIb and dDDH values below the species delineation thresholds. In agar diffusion assays, the crude extract exhibited antibacterial activity against Staphylococcus aureus (MSSA and MRSA), Bacillus subtilis, Bacillus cereus, Enterococcus faecalis, Staphylococcus epidermidis, as well as inhibition of Pseudomonas aeruginosa and Acinetobacter baumannii. LC–MS/MS profiling of the crude ethyl-acetate extract was performed. GNPS feature-based molecular networking revealed ions corresponding to actinomycin X2 (m/z 1269.6), D (m/z 1255.6), and I (m/z 1271.6), confirming production of multiple actinomycin analogs. These findings highlight Streptomyces sp. PSU-S4-23 as a promising actinomycin-producing strain with potential relevance to antibiotic discovery.