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

1
Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK
2
Department of Biology and Environmental Science, College of Science, University of the Philippines Cebu, Lahug, Cebu City 6000, Philippines
3
Department of Chemistry, University of Ghana, P.O. Box LG56 Legon-Accra, Ghana
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(10), 1464; https://doi.org/10.3390/biom10101464
Received: 16 September 2020 / Revised: 12 October 2020 / Accepted: 18 October 2020 / Published: 20 October 2020
(This article belongs to the Section Natural and Bio-inspired Molecules)
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 211, 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 113 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 113 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. View Full-Text
Keywords: accramycin; type II polyketides; Streptomyces sp. MA37; regulatory genes; gene inactivation; titer improvement; antibacterial activities; multidrug resistant Enterococcus accramycin; type II polyketides; Streptomyces sp. MA37; regulatory genes; gene inactivation; titer improvement; antibacterial activities; multidrug resistant Enterococcus
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MDPI and ACS Style

Maglangit, F.; Zhang, Y.; Kyeremeh, K.; Deng, H. Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37. Biomolecules 2020, 10, 1464. https://doi.org/10.3390/biom10101464

AMA Style

Maglangit F, Zhang Y, Kyeremeh K, Deng H. Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37. Biomolecules. 2020; 10(10):1464. https://doi.org/10.3390/biom10101464

Chicago/Turabian Style

Maglangit, Fleurdeliz, Yuting Zhang, Kwaku Kyeremeh, and Hai Deng. 2020. "Discovery of New Antibacterial Accramycins from a Genetic Variant of the Soil Bacterium, Streptomyces sp. MA37" Biomolecules 10, no. 10: 1464. https://doi.org/10.3390/biom10101464

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