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Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37.

ABSTRACT: Continued mining of natural products from the strain Streptomyces sp. MA37 in our laboratory led to the discovery of a minor specialized metabolite (SM) called accramycin A. Owing to its low yield (0.2 mg/L) in the wild type strain, we investigated the roles of regulatory genes in the corresponding biosynthetic gene cluster (acc BGC) through gene inactivation with the aim of improving the titer of this compound. One of the resulting mutants (?accJ) dramatically upregulated the production of accramycin A 1 by 330-fold (66 mg/L). Furthermore, ten new metabolites, accramycins B-K 2-11, were discovered, together with two known compounds, naphthacemycin B112 and fasamycin C 13 from the mutant extract. This suggested that accJ, annotated as multiple antibiotic resistance regulator (MarR), is a negative regulator gene in the accramycin biosynthesis. Compounds 1-13 inhibited the Gram-positive pathogens (Staphylococcus aureus, Enterococcus faecalis) and clinical isolates Enterococcus faecium (K59-68 and K60-39) and Staphylococcus haemolyticus with minimal inhibitory concentration (MIC) values in the range of 1.5-12.5 µg/mL. Remarkably, compounds 1-13 displayed superior activity against K60-39 (MIC = 3.1-6.3 µg/mL) compared to ampicillin (MIC = 25 µg/mL), and offered promising potential for the development of accramycin-based antibiotics that target multidrug-resistant Enterococcus clinical isolates. Our results highlight the importance of identifying the roles of regulatory genes in natural product discovery.

SUBMITTER: Maglangit F

PROVIDER: S-EPMC7590149 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37.

Maglangit Fleurdeliz F Zhang Yuting Y Kyeremeh Kwaku K Deng Hai H

Biomolecules 20201020 10

Continued mining of natural products from the strain Streptomyces sp. MA37 in our laboratory led to the discovery of a minor specialized metabolite (SM) called accramycin A. Owing to its low yield (0.2 mg/L) in the wild type strain, we investigated the roles of regulatory genes in the corresponding biosynthetic gene cluster (acc BGC) through gene inactivation with the aim of improving the titer of this compound. One of the resulting mutants (∆accJ) dramatically upregulated t ...[more]

PMID: 33092156

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Project description:The increasing concern over multidrug resistance in pathogens has led to an ongoing search for novel antibiotics derived from soil actinobacteria. In this current investigation, actinobacteria were isolated from the rhizosphere of bamboo plants collected within the Megamalai forest of the Western Ghats in the Theni zone of Tamil Nadu, India. These actinobacteria were subjected to characterization, and their growth conditions were optimized to enhance the production of bioactive compounds. To assess antibacterial properties, the isolated Actinobacteria underwent testing using the agar plug method. The strain exhibiting notable antibacterial activity underwent further characterization through 16s rRNA gene sequencing and subsequent phylogenetic analysis. Employing response surface methodology (RSM), cultural conditions were fine-tuned. Bioactive compounds were extracted from the culture medium using ethyl acetate, and their antibacterial and antioxidant effects were evaluated through disc diffusion and DPPH radical scavenging methods, respectively. Ethyl acetate extracts were analyzed by using FT-IR and GC-MS techniques. In total, nine strains of Actinobacteria were isolated from the rhizosphere soil of bamboo. Among these, strain BS-16 displayed remarkable antibacterial activity against three strains: Staphylococcus aureus (19 mm), Bacillus subtilis (12 mm), and Streptococcus pyogenes (10 mm). This strain was identified as Streptomyces sp. The optimal conditions for bioactive compound production were determined as follows: malt extract (10 g), yeast extract (5 g), dextrose (5 g), pH 6.5, and temperature 30 °C. After a 7-day incubation period, the results showed a 6% increase in production. The ethyl acetate fraction derived from strain BS-16 exhibited dose-dependent antibacterial and antioxidant activities. FT-IR and GC-MS analyses revealed the presence of active compounds with antibacterial effects within the extract. Consequently, further investigation into the BS-16 strain holds promise for scaling up the production of bioactive compounds possessing antibacterial and antioxidant properties.

Dataset Information

Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37.

Publications

Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, <i>Streptomyces</i> sp. MA37.

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